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Background: Obstructive sleep apnea (OSA) is one of the major co-morbidities and aggravating factors of asthma. In OSA-complicated asthma, obesity, visceral fat, and systemic inflammation are associated with its severity, but the role of bronchial hyperresponsiveness (BHR) is unclear. We investigated the involvement of BHR and mediastinal fat width, as a measure of visceral fat, with OSA severity in patients with OSA and asthma-like symptoms., Methods: Patients with OSA who underwent BHR test and chest computed tomography scan for asthma-like symptoms were retrospectively enrolled. We evaluated the relationship between apnea-hypopnea index (AHI) and PC 20 or anterior mediastinal fat width, stratified by the presence or absence of BHR., Results: OSA patients with BHR (n = 29) showed more obstructive airways and frequent low arousal threshold and lower mediastinal fat width, and tended to show fewer AHI than those without BHR (n = 25). In the overall analysis, mediastinal fat width was significantly positively correlated with AHI, which was significant even after adjustment with age and gender. This was especially significant in patients without BHR, while in OSA patients with BHR, there were significant negative associations between apnea index and airflow limitation, and hypopnea index and PC 20 ., Conclusions: Risk factors for greater AHI differed depending on the presence or absence of BHR in OSA patients with asthma-like symptoms. In the presence of BHR, severity of asthma may determine the severity of concomitant OSA., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: 27-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic inflammation in COPD. However, the role of regulation of CYP27A1- 27-HC axis in asthma is unclear. This study aimed to elucidate the contribution of the axis to the pathophysiology of asthma., Methods: House dust mite (HDM) extract was intranasally administered to C57BL/6 mice and the expression of CYP27A1 in the airways was analyzed by immunostaining. The effect of pre-treatment with PBS or CYP27A1 inhibitors on the cell fraction in the bronchoalveolar lavage fluid (BALF) was analyzed in the murine model. In vitro, BEAS-2B cells were treated with HDM and the levels of CYP27A1 expression were examined. Furthermore, the effect of 27-HC on the expressions of E-cadherin and ZO-1 in the cells was analyzed. The amounts of RANTES and eotaxin from the 27-HC-treated cells were analyzed by ELISA., Results: The administration of HDM increased the expression of CYP27A1 in the airways of mice as well as the number of eosinophils in the BALF. CYP27A1 inhibitors ameliorated the HDM-induced increase in the number of eosinophils in the BALF. Treatment with HDM increased the expression of CYP27A1 in BEAS-2B cells. The administration of 27-HC to BEAS-2B cells suppressed the expression of E-cadherin and ZO-1, and augmented the production of RANTES and eotaxin., Conclusions: The results of this study suggest that aeroallergen could enhance the induction of CYP27A1, leading to allergic airway inflammation and disruption of the airway epithelial tight junction through 27-HC production., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Objective: In Miyagi, the number of allergy specialists per population is higher at Sendai city compared to the other areas (non-Sendai areas). Therefore, the healthcare delivery for allergic diseases are unevenly distributed. In the current study, we investigated differences of medical care for allergic diseases between Sendai city and non-Sendai areas., Methods: We conducted a web-based questionnaire survey to all of hospitals and clinics in the prefecture. The questionnaire responses were analyzed and compared between the Sendai city and non-Sendai areas., Results: Responses to the questionnaire were obtained from 175 hospitals and clinics, including 72 internal physicians, 34 pediatricians, 17 dermatologists, 15 otorhinolaryngologists, 12 ophthalmologists and 25 others. More clinicians in non-Sendai areas felt the difficulty in treating asthma and chronic urticaria than those in Sendai city. Fewer institutions prescribed biologics for severe allergic diseases in non-Sendai areas than in Sendai city, which might be due to the lack of knowledge on the biologic agents. On the other hand, referring patients with anaphylaxis to specialized hospitals tended to be more difficult in Sendai city compared to in non-Sendai areas. Additionally, the regional medical liaison system is needed to refer patients with severe allergic diseases to advanced medical institutions., Conclusion: There are unique problems about allergy care in Miyagi.

Background: The airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens., Methods: BEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated., Results: The amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin., Conclusions: The current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.

We present a case of a 17-year-old woman with a history of bronchial asthma since two years of age. She had daily asthma attacks from the age of fourteen, and the addition of oral corticosteroids and omalizumab to regular inhaled corticosteroid inhalation failed to relieve symptoms. She was referred to our hospital for detailed examination. On admission, physical examination was normal, but she had complained of dyspnea at the round. Monophonic wheezes and stridor were heard over the anterior neck, while no rales were audible over any part of the chest. Laryngoscopy revealed paradoxical movement of the vocal cords, and a diagnosis of vocal cord dysfunction (VCD) was made. The apparent severe asthma symptoms were considered to reflect VCD, and the treatment for bronchial asthma was stepped down without any recurrence of asthma attacks. Although the etiology of the VCD was unknown, VCD is more common in young women, so stress and personality factors are thought to be involved. It has been noted that childhood asthma often improves between childhood and adolescence, but refractory cases have been noted. In intractable bronchial asthma cases, it is necessary to consider the complications of other diseases, such as VCD, and to perform appropriate management.

Background: We explored whether the use of deep learning to model combinations of symptom-physical signs and objective tests, such as lung function tests and the bronchial challenge test, would improve model performance in predicting the initial diagnosis of adult asthma when compared to the conventional machine learning diagnostic method., Methods: The data were obtained from the clinical records on prospective study of 566 adult out-patients who visited Kindai University Hospital for the first time with complaints of non-specific respiratory symptoms. Asthma was comprehensively diagnosed by specialists based on symptom-physical signs and objective tests. Model performance metrics were compared to logistic analysis, support vector machine (SVM) learning, and the deep neural network (DNN) model., Results: For the diagnosis of adult asthma based on symptom-physical signs alone, the accuracy of the DNN model was 0.68, whereas that for the SVM was 0.60 and for the logistic analysis was 0.65. When adult asthma was diagnosed based on symptom-physical signs, biochemical findings, lung function tests, and the bronchial challenge test, the accuracy of the DNN model increased to 0.98 and was significantly higher than the 0.82 accuracy of the SVM and the 0.94 accuracy of the logistic analysis., Conclusions: DNN is able to better facilitate diagnosing adult asthma, compared with classical machine learnings, such as logistic analysis and SVM. The deep learning models based on symptom-physical signs and objective tests appear to improve the performance for diagnosing adult asthma., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Asthma-chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet., Objectives: The aim of this study was to investigate nitrosative stress, which causes a redox imbalance and tissue inflammation in the airways of patients with ACO, and to evaluate the relationship between nitrosative stress and the clinical course in study subjects., Methods: Thirty healthy subjects and 56 asthmatic patients participated in this study. The asthmatic patients were divided into 33 asthmatic patients and 23 patients with ACO. The study subjects had been followed prospectively for 2 years to evaluate the clinical course. Nitrosative stress was evaluated based on the production of 3-nitrotyrosine (3-NT) in sputum cells., Results: Production of 3-NT was significantly enhanced in patients with ACO compared with that in asthmatic patients. Amounts of reactive persulfides and polysulfides, newly identified powerful antioxidants, were significantly decreased in the ACO group. Baseline levels of 3-NT were significantly correlated with the frequency of exacerbations and decrease in FEV 1 adjusted by age, smoking history, and blood eosinophil count. The 3-NT-positive cells were also significantly correlated with amounts of proinflammatory chemokines and cytokines., Conclusions: These findings suggested that greater nitrosative stress occurred in the airways of patients with ACO, and the degree of nitrosative stress was correlated with an impairment in the clinical course. Nitrosative stress might be related to the pathogenesis of ACO., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: We obtain summary estimates of the accuracy of additional objective tests for the diagnosis of adult asthma using systematic review and meta-analysis of diagnostic test accuracy studies., Methods: Medline, Embase, and other relevant electronic databases were searched for papers published between January 1989 and December 2016. Studies were included if they evaluated the diagnostic accuracy of objective tests, including airway reversibility (AR), airway hyperresponsiveness (AHR), and fractionated exhaled nitric oxide (FeNO) for the diagnosis of adult asthma in patients with symptoms suggestive of asthma. If papers were assessed appropriate using the adapted QUADAS-2 tool, meta-analysis was conducted using the hierarchical bivariate model. This hierarchical model accounts for both within and between study variability., Results: Sixteen studies reported the performance of the evaluated objective tests at presentation. For diagnosis of adult asthma, overall sensitivity and specificity for AR were 0.39 (95% confidence interval [CI] 0.18 to 0.66) and 0.95 (95% CI 0.86 to 1.00); for AHR, 0.86 (95% CI 0.61 to 1.00) and 0.95 (95% CI 0.77 to 1.00); for FeNO, 0.65 (95% CI 0.53 to 0.77) and 0.83 (95% CI 0.75 to 0.90). Comprehensive comparison of three diagnostic tools for adult asthma using the back-calculated likelihood rate (LR) showed that AR and AHR corresponded to a higher LR+, and AHR gave a lower LR-., Conclusions: In the current situation of no gold standard for diagnosis of adult asthma, AR and AHR are appropriate for ruling-in the true diagnosis, and AHR is superior for ruling-out a diagnosis. Since each objective test had a specific characteristic, it should be chosen depending on the situation, such as the capacity of the institution and the conditions of patients., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Ambient particulate matter (PM) can increase airway inflammation and induce bronchoconstriction in asthma. This study aimed to investigate the effect of tiotropium bromide, a long-acting muscarinic antagonist, on airway inflammation and bronchoconstriction induced by ambient PM in a mouse model of asthma. We compared the effect of tiotropium bromide to that of fluticasone propionate and formoterol fumarate. BALB/c mice were sensitized to ovalbumin (OVA) via the airways and then administered tiotropium bromide, fluticasone propionate, or formoterol fumarate. Mice were also sensitized to ambient PM via intranasal instillation. Differential leukocyte counts and the concentrations of interferon (IFN)-γ, interleukin (IL)-5, IL-6, IL-13, and keratinocyte-derived chemokine (KC/CXCL1) were measured in bronchoalveolar lavage fluid (BALF). Diacron-reactive oxygen metabolites (dROMs) were measured in the serum. Airway resistance and airway inflammation were evaluated in lung tissue 24 h after the OVA challenge. Ambient PM markedly increased neutrophilic airway inflammation in mice with OVA-induced asthma. Tiotropium bromide improved bronchoconstriction, and reduced neutrophil numbers, decreased the concentrations of IL-5, IL-6, IL-13, and KC/CXCL1 in BALF. However, tiotropium bromide did not decrease the levels of dROMs increased by ambient PM. Though eosinophilic airway inflammation was reduced with fluticasone propionate, neutrophilic airway inflammation was unaffected. Bronchoconstriction was improved with formoterol fumarate, but not with fluticasone propionate. In conclusion, tiotropium bromide reduced bronchoconstriction, subsequently leading to reduced neutrophilic airway inflammation induced by ambient PM., Competing Interests: The authors declare no conflict of interest.

Background and Objectives: Assessment of the effects of long-term management on patient quality of life (QOL) would be extremely useful for determining asthma treatment strategies. However, no studies have evaluated QOL over an extended period of time. This study evaluated the changes in QOL, drug management and disease severity in the same asthma patients at an interval of approximately 9 years., Methods: We re-surveyed asthma patients enrolled in a survey conducted in 2004 to evaluate the effects of approximately a decade of treatment on disease severity and QOL assessed by the Japanese Asthma Health Questionnaire (AHQ-JAPAN)., Results: A total of 2179 patients were enrolled in the study from 93 centres, and 1332 patients were included in the per-protocol analysis. Usage rates of inhaled corticosteroids (ICS) for treatment of stable asthma were over 90% at both time points. The AHQ-JAPAN total score improved significantly from 22.2±19.7 in 2004 to 19.7±19.9 in 2013 (P<.001). Significant improvements were also observed in 5 of 6 subscales of AHQ-JAPAN, with Social Activity constituting the sole exception., Conclusions: Asthma severity declined and QOL assessed by AHQ-JAPAN improved, which is considered as a reflection of improved asthma control at least partly attributable to widespread use of anti-inflammatory drugs as represented by ICS. The study also revealed the presence of those with poor QOL, especially in patients with concomitant respiratory diseases, and an increase in severe persistent asthma cases, warranting further long-term efforts at improving QOL., Trial Registration Number: UMIN 000010483., (© 2016 John Wiley & Sons Ltd.)

Asian dust (AD) can aggravate airway inflammation in asthma, but the association between AD and the development of asthma remains unclear. This study aimed to investigate the effects of AD on the early stage of antigen sensitization using a mouse model of asthma, as well as the role of leukotrienes (LTs) in antigen-induced airway inflammation potentiated by AD particles. NC/Nga mice were co-sensitized by intranasal instillation of AD particles and/or Dermatophagoides farinae (Df) for five consecutive days. Df-sensitized mice were stimulated with an intranasal Df challenge at seven days. Mice were treated with the type 1 cysteinyl LT (CysLT₁) receptor antagonist orally 4 h before and 1 h after the allergen challenge. At 24 h post-challenge, the differential leukocyte count, inflammatory cytokines, and LTs in bronchoalveolar lavage fluid were assessed, and airway inflammation was evaluated histopathologically. AD augmented neutrophilic and eosinophilic airway inflammation with increased CysLTs and dihydroxy-LT in a mouse model of asthma. The CysLT₁ receptor antagonist was shown to attenuate both neutrophilic and eosinophilic airway inflammation augmented by AD. Therefore, exposure to AD may be associated with the development of asthma and LTs may play important roles in airway inflammation augmented by AD., Competing Interests: The authors declare no conflict of interest.

This study aimed to investigate the effects of winter and spring particulate matter (PM) on airway inflammation and allergies in a mouse asthma model. PM was collected during 7-28 February 2013 (winter) and during 7-28 April 2013 (spring) in Yonago, Japan. NC/Nga mice were co-sensitized using intranasal instillation of the PMs and Dermatophagoides farinae (Df) for 5 consecutive days, and were subsequently challenged using intranasal Df at 7 days after the last sensitization. At 24 h after the challenge, serum immunoglobulin levels, differential leukocyte counts, and inflammatory cytokines levels were measured in the mice's bronchoalveolar lavage fluid (BALF). Compared to co-sensitization using spring PM and Df, winter PM and Df induced greater increases in the BALF neutrophil and eosinophil counts and total serum IgE and IgG2a levels. Furthermore, winter PM-sensitized mice exhibited higher BALF levels of interleukin-5, interleukin-13, interleukin-6, and keratinocyte-derived chemokine. Therefore, we observed seasonal variations in the effects of PM on asthma-related airway inflammation. These findings suggest that the compositions of PM vary according to season, and that it is important to evaluate PM compositions in order to understand the associations between asthma and PM.

Outdoor fungi are important components of airborne particulate matter (PM). However, the associations between pulmonary function and outdoor fungi are less well known compared to other airborne PM constituents. The objective of this study was to investigate the association between outdoor fungi and pulmonary function in children. Morning peak expiratory flow (PEF) rates were measured daily in 339 schoolchildren (including 36 with asthma), aged 10 to 12, 2 to 27 February 2015. Airborne PM was collected on filters, using a high volume air sampler, each day during the study period. The daily concentration of outdoor fungi-associated PM was calculated using a culture-based method. A linear mixed model was used to estimate the association between PEF values and daily concentrations of outdoor fungi, and the daily levels of suspended PM (SPM) and PM ≤ 2.5 μm (PM2.5). An increase in the interquartile range (46.2 CFU/m³) for outdoor fungal concentration led to PEF changes of -1.18 L/min (95% confidence interval, -2.27 to -0.08) in all children, 1.22 L/min (-2.96 to 5.41) in children without asthma, and -1.44 L/min (-2.57 to -0.32) in children with asthma. Outdoor fungi showed a significant negative correlation with PM2.5 levels (r = -0.4, p = 0.04), but not with SPM (r = ‒0.3, p = 0.10) levels. Outdoor fungi may be associated with pulmonary dysfunction in children. Furthermore, children with asthma may show greater pulmonary dysfunction than those without asthma.

Background: Asian dust (AD) has become a major health concern. The concentration of AD is typically expressed in particulate matter less than 10 μm (PM10) and 2.5 μm (PM2.5). However, PM10 and PM2.5 consist of various substances besides AD. Light detection and ranging (LIDAR) systems can selectively measure the quantity of AD particles to distinguish non-spherical airborne particles from spherical airborne particles. The objective of this study was to investigate the relationship between pulmonary function in adult asthma patients and AD using LIDAR data., Methods: Subjects were 231 adult asthma patients who had their morning peak expiratory flow (PEF) measured from March to May 2012. A linear mixed model was used to estimate the association of PEF with sand dust particles detected by LIDAR., Results: Increases in the interquartile range of AD particles (0.018 km(-1)) led to changes in PEF of -0.42 L/min (95% confidence interval [CI], -0.85 to 0.01). An increase of 11.8 μg/m(3) in suspended particulate matter and 6.9 μg/m(3) in PM2.5 led to decreases of -0.17 L/min (-0.53 to 0.21) and 0.03 L/min (-0.35 to 0.42), respectively. A heavy AD day was defined as a day with a level of AD particles >0.032 km(-1), which was the average plus one standard deviation during the study period, and six heavy AD days were identified. Change in PEF after a heavy AD day was -0.97 L/min (-1.90 to -0.04)., Conclusions: Heavy exposure to AD particles was significantly associated with decreased pulmonary function in adult asthma patients., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The characteristics of phenotypes of elderly patients with asthma are unknown. The aim of this study was to classify these phenotypes using lung function tests and images from high-resolution computed tomography (HRCT), and to identify associations between clinical characteristics and phenotypes., Methods: A cross-sectional study was conducted in 165 elderly patients (>65 years of age) who underwent a multidimensional assessment of clinical and functional status and comorbidity. The patients were divided into three phenotypes: (1) asthma-predominant, (2) asthma-obstructive airway disease (OAD) overlap without emphysema, and (3) asthma-OAD overlap with emphysema (asthma-emphysema overlap) based on chest HRCT. A receiver operating characteristic (ROC) curve was constructed to evaluate the cutoff for differentiating between the two OAD phenotypes. Multivariate analysis was also used to distinguish between these two phenotypes., Results: The phenotypes were asthma-predominant in 48 patients (29%), asthma-OAD without emphysema in 36 (22%), and asthma-emphysema in 81 (49%). Patients with asthma-emphysema were more frequent smokers. In multivariate analysis, smoking status (odds ratio 2.92: 95% CI 1.21-7.00, P = 0.03) and % predicted FEV1 ≤70% (odds ratio 3.18: 95% CI 1.13-8.92, P = 0.03) differed significantly between the asthma-emphysema and asthma-OAD without emphysema phenotypes., Conclusions: Half of elderly patients with asthma are characterized by asthma-emphysema overlap. Our results showed that elderly patients with asthma who are smokers and have moderate or severe OAD are also likely to have emphysema., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Asian dust (AD) exposure exacerbates pulmonary dysfunction in patients with asthma. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS), characterized by coexisting symptoms of asthma and chronic obstructive pulmonary disease, is considered a separate disease entity. Previously, we investigated the effects of AD on pulmonary function in adult patients with asthma. Here, we present the findings of our further research on the differences in the effects of AD exposure on pulmonary function between patients with asthma alone and those with ACOS., Methods: Between March and May 2012, we conducted a panel study wherein we monitored daily peak expiratory flow (PEF) values in 231 adult patients with asthma. These patients were divided into 190 patients with asthma alone and 41 patients with ACOS in this study. Daily AD particle levels were measured using light detection and ranging systems. Two heavy AD days (April 23 and 24) were determined according to the Japan Meteorological Agency definition. A linear mixed model was used to estimate the association between PEF and AD exposure., Results: Increments in the interquartile range of AD particles (0.018 km(-1)) led to PEF changes of -0.50 L/min (95% confidence interval, -0.98 to -0.02) in patients with asthma alone and -0.11 L/min (-0.11 to 0.85) in patients with ACOS. The PEF changes after exposure to heavy AD were -2.21 L/min (-4.28 to -0.15) in patients with asthma alone and -2.76 L/min (-6.86 to 1.35) in patients with ACOS. In patients with asthma alone, the highest decrease in PEF values was observed on the heavy AD day, with a subsequent gradual increase over time., Conclusion: Our results suggest that the effects of AD exposure on pulmonary function differ between patients with asthma alone and ACOS, with the former exhibiting a greater likelihood of decreased pulmonary function after AD exposure.

Although adult asthma is attributable to occupational factors and asthma and rhinitis are related, relatively few studies have investigated the prevalence of occupational rhinitis based on occupation, and knowledge of occupational rhinitis in Japan is currently limited. The objective of this cross-sectional study was to estimate the prevalence of allergic rhinitis among Japanese nursing professionals with asthma. A postal survey was conducted from October to December 2013 using translated versions of the European Community Respiratory Health Survey for the prevalence of asthma and State of the Impact of Allergic Rhinitis on Asthma Control questionnaire for the prevalence of rhinitis. Of 4,634 Japanese nursing professionals, 497 subjects had asthma, and 270 of these 497 subjects had allergic rhinitis (54.3%; 95% confidence interval [CI], 49.7-58.7). Latex allergy was significantly associated with allergic rhinitis (odds ratio, 1.77; 95% CI, 1.21-2.60). There was no relationship between employment period and prevalent allergic rhinitis. The results of this study provide fundamental information regarding occupational health among Japanese nursing professionals, including the prevalence of allergic rhinitis among Japanese nursing professionals with asthma and latex allergy as a potential risk factor for prevalent allergic rhinitis.

Objectives: Few reports are available concerning the prevalence of asthma among snow crab workers in Japan. The object of this study was to estimate the prevalence of asthma and wheezes among Japanese snow crab workers and their associations with exhaled nitric oxide (FeNO) and YKL-40., Methods: Forty-nine snow crab workers enrolled in this study, which was cross-sectional by design and was conducted using a translated version of the European Community Respiratory Health Survey questionnaire. The levels of FeNO and serum YKL-40 were measured between September and October 2014., Results: The prevalences of current asthma and wheezes were 10.2% (95% CI, 3.4 to 22.2) and 12.2% (95% CI, 4.6 to 24.8), respectively. There was no association between these prevalences and the duration of snow crab employment. Six subjects' FeNO levels exceeded 50 ppb, and nine subjects' levels exceeded 25 ppb. Twelve subjects' (25.5%) serum YKL-40 levels exceeded 77.2 ng/mL, which was 2 standard deviations above the mean for healthy subjects. However, there were no significant relationships among the prevalences for asthma and wheezes, FeNO, and serum YKL-40., Conclusions: This study provides information concerning the prevalences of asthma and wheezes among Japanese snow crab processing workers.

Although adult asthma is attributable to occupational factors, few reports are available on asthma prevalence among health care workers in Japan. The objective of this study was to estimate the prevalence of asthma and wheeze among Japanese nursing professionals. A cross-sectional study was conducted by postal survey using a translated version of the European Community Respiratory Health Survey questionnaire from April to June 2013. The analysis included 4634 nursing professionals (257 men and 4377 women) and the overall response rate was 84.8%. The prevalence of current asthma and wheeze were 10.7% (95% confidence interval (CI), 9.9%-11.7%) and 15.6% (95% CI, 14.5%-16.6%), respectively. More than one year of work experience as a nursing professional and more than one year of experience with bed-making tasks were associated with odds ratios (ORs) of 1.95 (95% CI, 1.12-3.39) and 1.64 (95% CI, 1.15-2.23) for wheeze, respectively. Current smoking was significantly associated with the presence of wheeze, with ORs of 2.27 for men (95% CI, 1.11-4.64) and 2.01 for women (95% CI, 1.54-2.64). Among female nurses, latex allergy was associated with wheeze (OR, 1.87; 95% CI, 1.56-2.23), as was body mass index ≥30 (OR, 2.76; 95% CI, 1.65-4.62). This study has provided the prevalence of asthma and wheeze among Japanese nursing professionals. Employment period, bed-making tasks, latex allergy, obesity, and smoking may be risk factors for prevalent wheeze among nursing professionals.

Light detection and ranging (LIDAR) can estimate daily volumes of sand dust particles from the East Asian desert to Japan. The objective of this study was to investigate the relationship between sand dust particles and pulmonary function, and respiratory symptoms in adult patients with asthma. One hundred thirty-seven patients were included in the study. From March 2013 to May 2013, the patients measured their morning peak expiratory flow (PEF) and kept daily lower respiratory symptom diaries. A linear mixed model was used to estimate the correlation of the median daily levels of sand dust particles, symptoms scores, and PEF. A heavy sand dust day was defined as an hourly concentration of sand dust particles of >0.1 km(-1). By this criterion, there were 8 heavy sand dust days during the study period. Elevated sand dust particles levels were significantly associated with the symptom score (0.04; 95% confidence interval (CI); 0.03, 0.05), and this increase persisted for 5 days. There was no significant association between PEF and heavy dust exposure (0.01 L/min; 95% CI, -0.62, 0.11). The present study found that sand dust particles were significantly associated with worsened lower respiratory tract symptoms in adult patients with asthma, but not with pulmonary function.

Background: Epidemiological investigations indicate that an Asian dust storm (ADS) can aggravate respiratory disorders. However, the effects of ADS on airway inflammation remain unclear. The aim of this study was to investigate the association of exposure to ADS with airway inflammation., Methods: The subjects were 33 adult patients with asthma who measured daily peak flow expiratory (PEF) from March to May 2012. Fractional exhaled nitric oxide (FeNO) was measured before and after ADS., Results: The FeNO values were 13.8±13.7 ppb before the ADS and 20.3±19.0 ppb after the ADS, with no significant difference. There was also no significant association of PEF with ADS exposure. However, the increase of FeNO after ADS exposure was proportional to the decrease of PEF (R=-0.78, P<0.0001)., Conclusion: These results suggest that airway inflammation aggravated by ADS exposure may induce a decrease in pulmonary function in some adult patients with asthma.

Objective: An Asian dust storm (ADS) contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil) in asthma model mice., Methods: Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df), and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured, and airway inflammation was examined histopathologically., Results: Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL)-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles., Conclusion: These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

Objective: Asian dust storms (ADS) contain various airborne particles that may augment airway inflammation by increasing the level of interleukin-8. The objective of the study was to investigate the association of exposure to an ADS with worsening of symptoms of adult asthma and the effect of ADS particles on interleukin-8 transcriptional activity., Methods: The subjects were 112 patients with mild to moderate asthma who recorded scores for their daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF) from March to May 2011. Interleukin-8 transcriptional activity was assessed in THP-G8 cells that were exposed to airborne particles collected during days of ADS exposure., Results: Of the 112 patients, 31 had comorbid allergic rhinitis (AR) and/or chronic sinusitis (CS), and had worsened scores for upper respiratory tract symptoms on ADS days compared to non-ADS days. Scores for lower respiratory tract symptoms during ADS days were higher than non-ADS days in all patients. Three patients also had unscheduled hospital visits for exacerbation of asthma on ADS days. However, there was no significant difference in daily morning PEF between ADS and non-ADS days. Airborne particles collected on ADS days induced interleukin-8 transcriptional activity in THP-G8 cells compared to the original soil of the ADS., Conclusion: Exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma. ADS airborne particles may increase airway inflammation through enhancement of interleukin-8 transcriptional activity.

Background: To predict the presence of asthma in adult patients with respiratory symptoms, we developed a scoring algorithm using clinical parameters., Methods: We prospectively analysed 566 adult outpatients who visited Kinki University Hospital for the first time with complaints of nonspecific respiratory symptoms. Asthma was comprehensively diagnosed by specialists using symptoms, signs, and objective tools including bronchodilator reversibility and/or the assessment of bronchial hyperresponsiveness (BHR). Multiple logistic regression analysis was performed to categorise patients and determine the accuracy of diagnosing asthma., Results: A scoring algorithm using the symptom-sign score was developed, based on diurnal variation of symptoms (1 point), recurrent episodes (2 points), medical history of allergic diseases (1 point), and wheeze sound (2 points). A score of >3 had 35% sensitivity and 97% specificity for discriminating between patients with and without asthma and assigned a high probability of having asthma (accuracy 90%). A score of 1 or 2 points assigned intermediate probability (accuracy 68%). After providing additional data of forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratio <0.7, the post-test probability of having asthma was increased to 93%. A score of 0 points assigned low probability (accuracy 31%). After providing additional data of positive reversibility, the post-test probability of having asthma was increased to 88%., Conclusions: This pragmatic diagnostic algorithm is useful for predicting the presence of adult asthma and for determining the appropriate time for consultation with a pulmonologist.

Background: Asthma has several phenotypical features, including recurrent exacerbations and recurrent episodes of upper respiratory infection (URI)., Purpose: A retrospective study was performed to identify the characteristics of adult patients with recurrent exacerbations of asthma, especially in association with recurrent episodes of URI., Methods: Information was collected using a self-administered questionnaire given to 7070 patients in autumn-winter 2006, 4859 patients in spring-summer 2007, and 4452 patients in autumn-winter 2007. The patients reported the degree of symptoms and the frequency of febrile episodes of URI and exacerbations. Severe exacerbations were defined as a self-report of asthma-related hospitalization, an emergency department visit, or a requirement for systemic corticosteroids. Recurrent febrile URI and exacerbations were defined as two or more episodes within the previous 6 months. A Poisson regression model was used to identify the factors that were predictors of a risk for exacerbations., Results: Of the 6266 patients who completed the questionnaire, the frequencies of febrile URI and episodes of severe exacerbations were 1.54 and 0.54 per subject per year, respectively. Logistic regression analysis showed that an older age [odds ratio (OR): 1.57; 95% confidence interval (CI): 1.15-2.13], female sex (OR: 1.58; 95% CI: 1.20-2.08), recurrent febrile episodes of URI (OR: 2.68; 95% CI: 1.47-4.91), a history of previous exacerbation within 1 year (OR: 1.74; 95% CI: 1.28-2.34), disuse of inhaled corticosteroids (ICSs) (OR: 2.63; 95% CI: 1.68-4.12), and disuse of add-on leukotriene receptor antagonists (LTRAs) (OR: 1.42; 95% CI: 1.06-1.74) were independently associated with moderate to severe symptom-severity. Poisson regression analysis showed that the independent factors that contributed to the frequency of recurrent severe exacerbations were female sex (regression coefficient β = 0.62, p < .01), an episode of sputum with coughing (β = 1.23, p < .01), nocturnal awakening (β = 1.22, p < .01), and severe exacerbation (β = 0.78, p < .01) within the previous 6 months., Conclusion: Symptom-severity of asthma and the frequency of severe exacerbations were associated with previous exacerbations and susceptibility to URI.

Background: Little is known about the role of the cysteinyl leukotriene (cysLT) 2 receptor in the pathophysiology of asthma. The aim of this study is to investigate the effects of a cysLT1 receptor antagonist (montelukast) and a dual cysLT1/2 receptor antagonist (BAY-u9773) on airway hypersensitivity and airway inflammation induced by antigen challenge in ovalbumin (OVA)-sensitized guinea pigs., Methods: Male Hartley guinea pigs sensitized with OVA were intraperitoneally administered 0.1, 1, or 10 mg/kg of montelukast or 0.1 mg/kg of BAY-u9773 and then challenged with inhaled OVA. Airway reactivity to acetylcholine, inflammatory cells in bronchoalveolar lavage (BAL) fluid, and eosinophil infiltration in airway walls after OVA challenge were evaluated., Results: Pretreatment with 1 or 10 mg/kg, but not 0.1 mg/kg, of montelukast significantly suppressed airway hypersensitivity and eosinophil infiltration into the BAL fluid. Moreover, 0.1 mg/kg of BAY-u9773 significantly suppressed the development of these markers. The suppressive effects of BAY-u9773, although not significantly different, trended toward being greater than those of montelukast. Although all of the doses of montelukast tested and 0.1 mg/kg of BAY-u9773 significantly suppressed eosinophil infiltration in airway walls, the suppressive effect of BAY-u9773 was significantly greater than that of 0.1 mg/kg of montelukast., Conclusion: Signaling may contribute to the pathophysiology of asthma via the cysLT1/2 receptor., (Copyright © 2011 S. Karger AG, Basel.)

Salivary pH is associated with esophageal acid reflux and neutralization of esophageal acid. In this study, we assessed the association between nocturnal decline of salivary pH and airway hyperresponsiveness. Salivary pH was serially assessed in 9 patients with mild asthma (7 men and 2 women; mean age 33.3 years; mean %predicted FEV(1.0) 89.4%) and 10 healthy volunteers (6 men and 4 women; mean age 31.2 years) using a pH indicator tape. The buffering capacity of saliva was defined as the median effective dose (ED(50)) for acidification of saliva with 0.01 N HCl, and airway responsiveness was defined as the dose of methacholine producing a 35% fall in Grs (PD(35)-Grs). There was a significant correlation between the values obtained from the pH indicator tape and those obtained from the electrometric pH meter. Using the indicator tape for sequential monitoring, we observed a nocturnal fall (ΔpH) in salivary pH in all subjects. A significant correlation was found between airway hyperresponsiveness (PD(35)-Grs) and either ΔpH or ED(50) in mildly asthmatic patients. Vagal reflux dysfunction might contribute to nocturnal salivary pH as well as to airway hyperresponsiveness in mild asthmatics.

We previously reported that intranasal challenge with ovalbumin (OVA) plus IL-18 induces airway hyperresponsiveness (AHR) and eosinophilic airway inflammation in mice with OVA-specific T(h)1 cells. These two conditions can be prevented by neutralizing anti-IFN-gamma and anti-IL-13 antibodies, respectively. The mice develop AHR and eosinophilic airway inflammation after challenge with OVA plus LPS instead of IL-18 and endogenous IL-18 is known to be involved. In contrast, IL-18 does not facilitate these changes in mice possessing OVA-specific T(h)2 cells. Here, we investigated whether IL-18 is involved in the development of asthma in mice immunized and challenged with bacterial proteins. Upon intranasal exposure to protein A (SpA) derived from Staphylococcus aureus, mice immunized with SpA exhibited AHR and peribronchial eosinophilic inflammation if IFN-gamma or IL-13 were present, respectively. The CD4(+) T cells from draining lymph nodes (DLNs) of the SpA-immunized and -challenged mice produced a robust IFN-gamma and IL-13 in response to immobilized anti-CD3 antibodies. Treatment with neutralizing anti-IL-18 antibodies prevented asthmatic inflammation concomitant with their impaired potential to express IFN-gamma and IL-13. Furthermore, naive mice that received the CD4(+) T cells from DLNs of SpA-immunized mice developed airway inflammation depending upon the presence of IL-18. Immunodeficient mice that received human PBMCs, which had been stimulated with SpA in vitro, developed dense peribronchial accumulation of human CD4(+) T cells upon SpA challenge. Neutralizing anti-human IL-18 antibodies protected against this airway inflammation. These results suggest the importance of IL-18 for the development of asthmatic inflammation associated with airway exposure to bacterial proteins.

Background: Various factors have been reported to be useful for predicting future exacerbations., Objective: This study was intended to determine a usefulness of a combination of a patient-based questionnaire, such as the Asthma Control Test (ACT) score with objective assessments, such as forced expiratory volume in 1 second (FEV(1)) and/or exhaled nitric oxide (FE(NO)), for predicting future exacerbations in adult asthmatics., Methods: We therefore enrolled 78 subjects with mild to moderate asthma, who were clinically stable for 3 months who all had been regularly receiving inhaled steroid treatment. All subjects underwent a routine assessment of asthma control including the ACT score, spirometry, and FE(NO), and then were followed up until a severe exacerbation occurred. The predictors of an increased risk of severe exacerbation were identified and validated using decision trees based on a classification and regression tree (CART) analysis. The properties of the developed models were the evaluated with the area under the ROC curve (AUC) (95% confidence interval [CI])., Results: The CART analysis automatically selected the variables and cut-off points, the ACT score

Bronchial asthma is a chronic inflammatory disorder of the airways, in which inflammation causes bronchial hyper-responsiveness and flow limitation in the presence of various stimuli. Pulmonary function in asthmatic patients frequently deteriorates between midnight and early morning, which has suggested a role for chronotherapy. Although relationships between bronchial asthma and the function of clock genes remain unclear, some medications given for asthma such as glucocorticoids or beta(2)-adrenoceptor agonists may influence clock genes in vivo. In our studies of clock gene mRNA expressions in human bronchial epithelial cells in vitro and peripheral blood cells in vivo, we demonstrated that glucocorticoid or beta(2)-adrenoceptor agonist treatment strongly induced human Per1 mRNA expression both in vitro and in vivo. Human peripheral blood cells provide a useful indication of peripheral clock gene mRNA expression in vivo.

Background and Aim: Revised guidelines were released in Japan in 2003 for the assessment, treatment, and management of adult asthmatics, and similar guidelines for child asthmatics were released in 2002. We reassessed the severity and possible undertreatment of asthma according to these guidelines in stable asthmatics., Methods: We reviewed medical records of 861 well-controlled asthmatic patients who, in April through June 2004 were cared for by 47 pulmonologists at 29 medical centers and 13 asthma clinics in a rural community in the San-in area of Japan. The physician obtained completed medical records about their symptoms and current treatment of the subjects, 726 adult and 135 children (aged 6 years or older) who were in stable condition and had had no exacerbations in the previous 3 months. The severity of asthma and current treatment for each patient were assessed according to the newly revised Japanese guidelines for the assessment, treatment, and management of adult and child asthmatics., Results: In adult and child asthmatics, the percentage of predicted forced expiratory volume at 1 second (FEV1.0) was smaller and has a narrower distribution range than the percentage of predicted peak expiratory flow (PEF). When the severity of asthma was classified according to symptoms alone, 50% and 35% of those classified as mildly asthmatics patients with adults and children, respectively, had moderate to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of adult and 14.9% of child patients. When we compared the treatments that patients were actually receiving against the optimal treatments indexed according to a combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics were overtreated, 21% were properly treated, and 30% were undertreated. Among children, the respective percentages were 35%, 25%, and 40%., Conclusion: In well-controlled adult and child asthmatics, the severity of asthma is poorly judged when symptoms alone are considered. We suggest that the severity of asthma should be assessed through a combination of symptoms and the measurement of FEV1.0 during office visits. We also suggest that the proper dose of inhaled steroid needed to maintain stable conditions should be judged according to this combined symptoms-FEV1.0 classification.

The aim of the study was to characterize patients at risk for exacerbations of their asthma as a result of the Tottori-Ken Seibu earthquake and to identify factors that predict exacerbation of asthma after an earthquake. A retrospective cohort study-analysis was conducted of 156 asthmatic patients, aged 18 to 89 years, who were out-patients of Tottori University Hospital and who had completely recorded their asthmatic symptoms and measured their peak expiratory flow (PEF) rates for more than one year prior to the earthquake. Seventeen (11%) patients who experienced the earthquake were identified as having an exacerbation within one month after the earthquake. Diurnal variability of PEF during the month after the earthquake was compared to values during a matched month one year previously. When factors associated with exacerbation were identified by a review of the medical case notes and the contribution of these factors to the exacerbation was determined using multivariate analysis, airflow limitation was shown to be independently associated with exacerbation after the earthquake. Acute asthma attacks are more likely to occur within the first week after the earthquake event without diurnal PEF variability. Asthma is likely to worsen after an earthquake.

The chronic inflammation of bronchial asthma is characterized by swelling of the subepithelial mucosa. However, it is difficult to assess subepithelial edema clinically. We report the case of a patient with asthma whose subepithelial edema was evaluated by endobronchial ultrasonography. Receiving montelukast 10 mg/day for 2 weeks, a 42-year-old man with mild, persistent asthma had his symptoms controlled by beta2-inhalation alone. Pretreatment endobronchial ultrasonography revealed subepithelial thickening in the right main stem bronchus, with a low absorption area suggestive of edema. Two weeks of montelukast therapy diminished the amount of subepithelial edema. Endobronchial ultrasonography is a promising technique for determining subepithelial edema in the asthmatic airway.

Genes of the IL-1 family encode three different peptides, IL-1alpha, IL-1beta, and IL-1Ra, respectively. IL-1 operates through IL-1RI, and is involved in airway inflammation in asthmatic subjects, whereas IL-1Ra appears to be a specific competitive inhibitor of IL-1. All genes are on chromosome 2q12-21 where genomewide searches have identified linkage for asthma. To test whether variants of IL-1 relate to asthma, we conducted a genetic association study in a Japanese population. We show that the A2 allele of IL1RN (encoding IL-1Ra) associates with nonatopic asthma [OR = 5.71, 95% CI: 1.63-19. 8, Pc = 0.007]. Both atopic and nonatopic asthmatics with the A2 allele had significantly lower serum IL-1Ra levels in both types of asthmatics. Peripheral blood cells from asthmatics with A2 alleles, however, produced as much IL-1 as did those with A1 homozygotes. Since Th1 and Th2 cytokines differentially regulate the ratio between IL-1beta and IL-1Ra, these findings suggest that dysregulation of IL-1beta/IL-1Ra, probably due to interaction between epithelium and immuno-competent cells in the airway, is important in asthma inflammation., (Copyright 2000 Academic Press.)

The aim of this study was to determine which background variables exert the most influence on airway responsiveness in adult asthmatic patients. The relationships between airway response and background variables were investigated by multiple linear and logistic regression analysis in 97 asthmatic patients. Airway responsiveness was measured by the oscillation technique during methacholine inhalation challenge. The regression analyses revealed that modified Aas score "one of asthma severity score", was the major factor contributing to airway hyperreactivity. We conclude that the number of attacks during a previous year is the most important background factor related to airway hyperresponsiveness on a clinical basis.

Activated mononuclear cells (lymphocytes and monocytes) (MNCs) circulate in peripheral blood and accumulate in the airways of individuals with steady-state asthma. The expression of adhesion molecules on MNCs of 10 patients with steady-state atopic asthma and 10 non-atopic control subjects was measured by flow cytometry. The mean fluorescence intensity of CD23 (P = 0.0003), CD11a (P = 0.034), and very late antigen-4 (VLA-4) (P = 0.016) was increased on lymphocytes of asthmatic patients relative to those of controls. Although the expression of CD16 (P = 0.002) and CD23 (P = 0.002), which are associated with differentiation into macrophages, was increased on monocytes of patients relative to those of controls, monocyte expression of VLA-4 (P = 0.006) and sialyl Lewis x (P = 0.005) was reduced. The concentration of interleukin-4 (IL-4) in serum was significantly higher in asthmatic patients than in normal subjects (P = 0.023), and a significant correlation was apparent between the serum concentration of IL-4 and the expression of VLA-4 on lymphocytes (p = 0.71, P = 0.03) or on monocytes (p = -0.72, P = 0.03) in asthmatic patients. Results suggest that IL-4 may contribute to the priming of adhesion molecule expression on lymphocytes even in steady-state conditions in individuals with chronic allergic inflammation.

Students who had asthma in childhood can be divided into three groups: "asthma-remission" group "asthma-relapsing" group and "non-asthma-remission" group. When we made inquiries about three different groups, the incidence of each group was 58%, 27% and 15%, respectively. In order to determine if childhood asthma affects respiratory function in adulthood, we measured respiratory functions by spirometry in 26 students who had asthma in childhood, and in seven control students. There was no significant difference between students with childhood asthma and control students in terms of FEV1.0% of predicted value. However, students who had asthma in childhood had lower levels of V25/HT% of predicted value in comparison with control students. The effects of deep inhalation in the three groups were evaluated by determining the values of maximal expiratory flow at 40% (MEF40) of vital capacity from partial (P) and maximal (M) flow-volume curves. There was no difference between the remission group and the control group in the MEF40 M/P ratio. This suggests that childhood asthma may deteriorate respiratory functions in adulthood by remodeling of peripheral airways.

Abstract Background Asthma is characterised by increased numbers of Th2-like cells in the airways and IgE secretion. Generation of Th2 cells requires interleukin (IL)-4 and IL-13 acting through their specific receptors and activating the transcription factor, signal transducer and activator of transcription 6 (STAT6). STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a critical role for STAT6 in allergic responses. Methods We have investigated the expression of STAT6 in peripheral blood T-lymphocytes, alveolar macrophages and bronchial biopsies from 17 normal subjects and 18 mild-moderate steroid-naïve stable asthmatic patients. Results STAT6 expression was variable and was detected in T-lymphocytes, macrophages and bronchial epithelial cells from all subjects with no difference between normal and stable asthmatic subjects. Conclusions STAT6 expression in different cells suggests that it may be important in regulating the expression of not only Th2-like cytokines in T cells of man, but may also regulate STAT-inducible genes in alveolar macrophages and airway epithelial cells.