Search

Background: TRAVERSE (NCT02134028), a phase 3 open-label extension study, assessed dupilumab safety and efficacy in patients with asthma aged ≥12 years who completed a previous dupilumab asthma study. This analysis evaluated changes in multiple lung function parameters in patients with moderate-to-severe asthma with elevated type 2 biomarkers (baseline eosinophils ≥150 cells·μL -1 or fractional exhaled nitric oxide ≥25 ppb) who completed QUEST (parent study) and 2 years of dupilumab treatment in TRAVERSE., Methods: Endpoints analyzed included: pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), forced expiratory flow (FEF 25 - 75 % ), and pre- and post-bronchodilator FEV 1 /FVC at parent study baseline (PSBL) at Weeks 0, 2, 48, and 96 in TRAVERSE, as well as pre- and post-bronchodilator FEV 1 slopes in QUEST and TRAVERSE. Statistical analyses were descriptive., Results: Dupilumab improved pre-bronchodilator FEV 1 , FVC, and FEF 25-75 % in QUEST; these improvements were sustained in TRAVERSE. In QUEST patients who received placebo, dupilumab initiation in TRAVERSE resulted in rapid lung function improvements. Mean (standard deviation) changes from PSBL at TRAVERSE Weeks 48 and 96 in pre-bronchodilator FEV 1 were 0.52 (0.59) and 0.45 (0.49) L in the dupilumab/dupilumab group and 0.47 (0.42) and 0.44 L (0.45) in the placebo/dupilumab group, respectively. Similar trends were observed for FVC and FEF 25-75 % . Dupilumab also improved FEV 1 slopes in QUEST and TRAVERSE., Conclusion: Dupilumab demonstrated sustained improvements across multiple spirometric lung function measurements for up to 3 years; patients who received placebo in QUEST experienced rapid lung function improvement upon initiation of dupilumab in TRAVERSE., Competing Interests: Declaration of competing interest A. Papi reports grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, and Teva; personal fees and non-financial support from Menarini, Novartis, and Zambon; and grants from Sanofi. M. Castro reports research support from the American Lung Association, AstraZeneca, GSK, NIH, Novartis, PCORI, Pulmatrix, sanofi-aventis, and Shionogi; consultancy fees from Genentech, Novartis, sanofi-aventis, and Teva; speaker fees from AstraZeneca, Genentech, GSK, Regeneron Pharmaceuticals, Inc., Sanofi and Teva; and royalties from Elsevier. J. Corren reports research grants from AstraZeneca, Genentech, Novartis and Regeneron Pharmaceuticals Inc.; research grants and consultancy fees from Sanofi; and speaker fees from AstraZeneca, Genentech, and Novartis. I.D. Pavord reports speaker fees from Aerocrine, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Teva; payments for organizing educational events from AstraZeneca and Teva; consultancy fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals Inc., RespiVert, Sanofi, Schering-Plough, and Teva; international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, and Teva; and research grants from Chiesi. Y. Tohda reports consultancy fees from AstraZeneca, Kyorin Pharmaceutical, Novartis, Sanofi, and Teijin Pharma. A. Altincatal, N. Pandit-Abid, E. Laws, L.P. Mannent, J.A. Jacob-Nara, P.J. Rowe, and M. Hardin are employees of Sanofi and may hold stock and/or stock options in the company. B. Akinlade, R. Gall, Y. Deniz, and D.J. Lederer are employees and shareholders of Regeneron Pharmaceuticals Inc., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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: Patients with idiopathic pulmonary fibrosis (IPF) have a slowly progressive clinical course, although some develop acute exacerbations (AEs). An easily obtained composite score is desirable for predicting the survival rate in patients with AE of IPF (AE-IPF). We investigated the quick sequential organ failure assessment (qSOFA), originally developed to identify sepsis, as a predictor of mortality in patients with AE-IPF and compared it to other composite assessments., Methods: Consecutive patients with IPF admitted for their first AE between 2008 and 2019 were recruited retrospectively. The association between the qSOFA score obtained at admission and mortality was investigated., Results: During the study period, 97 patients with AE-IPF were hospitalized. The hospital mortality was 30.9%. Multivariate logistic regression analysis revealed that both the qSOFA and the Japanese Association for Acute Medicine (JAAM)-disseminated intravascular coagulation (DIC) scores were significant predictors of hospital mortality (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.43-10.3; p = 0.007 and OR 2.71, 95% CI 1.56-4.67; p = 0.0004; respectively). Kaplan-Meier survival curves showed that both scores were consistently associated with survival. Furthermore, the sum of the two scores was a more effective predictor than the individual scores., Conclusions: The qSOFA score of patients admitted with AE-IPF was associated with both in-hospital and long-term mortality, which was also true for the JAAM-DIC score. The qSOFA score plus the JAAM-DIC score should be determined during the diagnostic evaluation of a patient with AE-IPF. Both scores combined may be more effective at predicting outcomes than individual scores., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Safety and efficacy data for dupilumab beyond 1 year are lacking for patients from Japan with moderate-to-severe asthma., Methods: The TRAVERSE open-label extension (OLE) study (NCT02134028) assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in 2282 patients who completed a previous dupilumab asthma study. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints included annualized severe exacerbation rate and change from parent study baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV 1 ), asthma control, quality of life, and blood eosinophil levels. Anti-drug antibodies (ADA) were evaluated. We report results in 160 (7.8% of exposed population) patients recruited from Japanese centers with non-oral corticosteroid (OCS)-dependent asthma rolled over from two parent studies, and in subgroups with a type 2 inflammatory phenotype., Results: TEAEs were consistent with the parent studies and the known safety profile of dupilumab. One patient permanently discontinued treatment due to TEAEs. Exacerbation rates remained low and were sustained to Week 96, as were improvements in pre-bronchodilator FEV 1 . Rapid, sustained improvements were observed in dupilumab-treated patients who previously received placebo in a parent study, while further improvements in exacerbation rates, asthma control, and asthma-related quality of life were observed in those continuing dupilumab. Blood eosinophil levels decreased progressively while on treatment. Treatment-emergent ADA responses were highest in patients who had previously received placebo. Efficacy results were consistent in patients with a type 2 phenotype., Conclusions: Long-term dupilumab treatment was well tolerated and efficacious in patients with non-OCS-dependent, moderate-to-severe asthma recruited from Japan. (Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov identifier, NCT02134028)., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is diagnosed incidentally in some patients with minimal or no respiratory symptoms. The clinical features of such patients are unknown. Herein we aimed to clarify the prevalence, clinical course, and prognostic factors of patients who were incidentally diagnosed with IPF., Methods: The files of consecutive patients with newly diagnosed IPF were retrospectively reviewed to determine the methods involved in their diagnosis, and their outcomes., Results: Among a total of 107 patients with newly diagnosed IPF, 35 (32.7%) were diagnosed incidentally, including 18 undergoing annual health check-ups and 17 undergoing assessment for other medical problems. The median survival from the time of diagnosis was 4.9 years for the 35 patients diagnosed incidentally, which was comparable to the median survival of 3.9 years for the 72 who were not diagnosed incidentally. The body mass index (BMI) was the sole independent predictor of survival (hazard ratio 0.78, 95% confidence interval 0.65-0.93, p = 0.006) in patients diagnosed incidentally., Conclusions: Nearly one third of patients with IPF were diagnosed incidentally, and their survival was still poor. Identifying patients during the earliest stage of IPF, particularly those with a low BMI, is warranted., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare in relation to the article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Clinical trials have shown treatment benefits of dupilumab in patients with uncontrolled asthma for up to 1 year. This study aimed to evaluate the long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma, as data for extended treatment with dupilumab beyond 1 year are not available., Methods: TRAVERSE was an open-label extension study in 362 hospitals and clinical centres across 27 countries that assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in adults and adolescents (aged 12-84 years) with moderate-to-severe or oral-corticosteroid-dependent severe asthma who had completed a previous dupilumab asthma study (phase 2A EXPEDITION, phase 2B DRI [P2b], phase 3 QUEST, or VENTURE). The primary endpoint was the number and percentage of patients with any treatment-emergent adverse events. Secondary endpoints included annualised exacerbation rate (AER) over the treatment period and change from parent study baseline in pre-bronchodilator FEV 1 , the five-item asthma control questionnaire (ACQ-5), the asthma quality of life questionnaire (AQLQ), type 2 biomarkers (blood eosinophils and serum total IgE), and anti-drug antibodies (ADAs). Statistical analyses were descriptive. We report safety in all enrolled patients, and efficacy in patients with non-oral-corticosteroid-dependent asthma and in subgroups, including patients with a type 2 inflammatory phenotype who received 148 weeks of treatment. This study is registered with ClinicalTrials.gov, NCT02134028., Findings: Between Aug 5, 2014, and Oct 11, 2019, of 2302 patients assessed for eligibility, 2282 adults and adolescents were enrolled (median age 50 years, 62·1% female and 37·9% male). Safety during TRAVERSE was consistent with the known dupilumab safety profile. The proportion of patients reporting treatment-emergent adverse events throughout the study duration was similar to that observed in the parent studies and ranged from 76·3% to 94·7%. The most frequently reported treatment-emergent adverse events were nasopharyngitis (17·5-25·9%), injection-site erythema (2·2-23·4%), and bronchitis (9·3-19·0%). Serious asthma exacerbations (0·5-3·6%) and pneumonia (0·7-2·7%) were the most frequently reported serious adverse events. There were four treatment-emergent adverse events leading to death. Efficacy during TRAVERSE was also consistent with the results of parent studies. In patients who were non-oral-corticosteroid-dependent, AER remained low (0·277-0·327) across parent study and treatment groups, pre-bronchodilator FEV 1 improvements were sustained to the end of treatment at week 96 (mean changes from parent study baseline ranged from 0·22 L [SD 0·44] to 0·33 L [0·44] across parent study and treatment groups), and improvements in ACQ-5 and AQLQ scores were sustained to the last timepoint assessed at week 48. Rapid improvements were observed in pre-bronchodilator FEV 1 and sustained improvements were seen in all outcome measures for patients given dupilumab who previously received placebo in parent studies; further improvements in AER, asthma control, and health-related quality of life were observed in patients who continued receiving dupilumab. Blood eosinophils and serum total IgE decreased progressively. ADA status had no effect on safety or efficacy. In the subgroup of patients with a type 2 inflammatory phenotype followed-up for 148 weeks, AER decreased progressively, and initial lung function improvements were sustained over 148 weeks., Interpretation: Data show that safety and efficacy of dupilumab in adult and adolescent patients with moderate-to-severe asthma are sustained when treatment is extended up to 148 weeks. These findings therefore support the long-term use of dupilumab in this patient population., Funding: Sanofi and Regeneron Pharmaceuticals., Competing Interests: Declaration of interests MEW reports personal fees from AstraZeneca, Boehringer Ingelheim, Equillium, Gala Therapeutics, Genentech, Genzyme, Mylan, Novartis, Pulmatrix, ResTORbio, Regeneron Pharmaceuticals, Sentien Biotechnologies, and Teva; and grants and personal fees from GSK and Sanofi. LBF reports grant support through the Asthma & Allergy Center, Bellevue, NE, USA, from 3M, Aimmune, AstraZeneca, DBV Technologies, Genentech, Glenmark, GSK, Hoffmann-La Roche, Novartis, Pearl, Sanofi, and Teva; and has served as a national consultant for Sanofi. JFM has served as a consultant for AstraZeneca and Sanofi; received speaker fees from Boehringer Ingelheim, GSK, Menarini, Novartis, and Uriach; and received research grants from Novartis. IDP reports speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi, and Teva; payments for organisation of educational events from AstraZeneca, GSK, Regeneron Pharmaceuticals, Sanofi, and Teva; consultant fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, RespiVert, Sanofi, Schering-Plough, and Teva; international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi, and Teva; and a research grant from Chiesi. AP reports grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, and Teva; personal fees and non-financial support from Menarini, Novartis, and Zambon; and grants from Sanofi. AB reports non-financial support during the conduct of the study from GSK; serving as an investigator on clinical trials promoted by Acceleron Pharma, Actelion, Galapagos, MSD, Nuvaira, Pulmonx, United Therapeutic, and Vertex Pharmaceuticals; grants and personal fees from Boehringer Ingelheim; and personal fees from AstraZeneca, Chiesi, GSK, Regeneron Pharmaceuticals, and Sanofi. HW reports serving as a consultant and receiving travel and speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Novartis, Sanofi, and Takeda. MC reports research support from the American Lung Association, AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, Patient-Centered Outcomes Research Institute, and Sanofi; serving as a consultant for 4D Pharma, Aviragen Therapeutics, Boston Scientific, Genentech, Nuvaira, Sanofi, Teva, Therabron Therapeutics, Theravance Biopharma, Vectura, and Vida Pharma; speaker fees from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Genentech, Regeneron Pharmaceuticals, Sanofi, and Teva; and royalties from Elsevier. NMN reports speaker fees from ALK, AstraZeneca, Boehringer Ingelheim, Glenmark, MSD, Novartis, Sanofi, Stallergenes Greer, and Teva. YT has served as a consultant for AstraZeneca, Kyorin Pharmaceuticals, and Sanofi. DL has received research funding from Sanofi. CD reports travel and speaker fees from Allergy Therapeutics, ALK, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GSK, HAL Allergy, Inmunotek, Menarini, Novartis, Pfizer, Sanofi-Aventis, Stallergenes Greer, Takeda, and Teva. KRC reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Genentech, Grifols, Kamada, Mereo BioPharma, Novartis, Roche, and Sanofi; grants from Amgen, Baxter, and GSK; and personal fees from the GSK-Canadian Institutes of Health Research chair in Respiratory Health Care Delivery at the University Health Network, and Merck. XM, AHK, PJR, UK, LPM, EL, and MH are Sanofi employees and hold stock or stock options in the company. YZ, YD, FAK, MR, and NA are employees and shareholders at Regeneron Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Asthma patients often feel satisfied with their current treatment, even when they have been diagnosed as uncontrolled by physicians. The present study investigated the differences in the evaluation of asthma control levels between patients and physicians, and the prediction of future risks., Methods: Asthma patients receiving inhaled corticosteroid/long-acting beta-2 agonists for 4 weeks or more were enrolled and followed-up for 24 weeks. Asthma control levels were evaluated using the following guidelines: Asthma Prevention and Management Guideline, Japan (JGL) and Global Initiative for Asthma (GINA) by physicians, and the Japan Asthma Control Survey (JACS) and a 6-item Asthma Control Questionnaire (ACQ6) by patients, at weeks 0 and 24. Analysis for predictive factors influencing exacerbation was performed using JGL, GINA, JACS, and ACQ6 at week 0., Results: A total of 420 patients were enrolled. Comparison of the distribution of asthma control levels assessed by physicians and patients showed no statistically significant difference between JGL and JACS (P = 0.19), suggesting a symmetric distribution, while ACQ6 demonstrated a significant difference versus JGL and GINA (both P < 0.001). The predictive factors for exacerbation were unscheduled visits based on GINA (rate ratio; 0.25, 95% CI; 0.14, 0.44), and the use of oral steroids on 3 consecutive days based on JGL (rate ratio; 0.42, 95% CI 0.22, 0.82) and JACS (rate ratio; 0.22, 95% CI; 0.13, 0,40)., Conclusions: Our study suggests that evaluation based on treatment guidelines and the questionnaire validated according to the local treatment guidelines is important for improved assessment of asthma control levels and the reduction of future risk., Clinical Trial Registration Number: UMIN000030419., Competing Interests: Conflict of Interest TI has received honoraria from Kyorin Pharmaceutical and research funding from Kyorin pharmaceutical, Meiji Seika Pharma, Boehringer Ingelheim, Teijin Pharma, Daiichi Sankyo, Astellas Pharma, and Pearl Therapeutics Inc. HT has received honoraria from GlaxoSmithKline, AstraZeneca, and Kyorin Pharmaceutical. SH has received honoraria from Astellas Pharma, GlaxoSmithKline, Novartis Pharma, AstraZeneca, Boehringer Ingelheim, Kyorin Pharmaceutical, and Sanofi. YT has received honoraria from Kyorin Pharmaceutical and Teijin Pharma and grant/research funding from Kyorin Pharmaceutical, Meiji Seika Pharma, Boehringer Ingelheim, Teijin Pharma, Daiichi Sankyo, Astellas Pharma, and Pearl Therapeutics Inc., (Copyright © 2021. Published by Elsevier B.V.)

Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts., Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables?, Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC)., Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV 1 , 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy., Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with idiopathic pulmonary fibrosis (IPF) are at risk of acute exacerbations (AEs) that manifest as respiratory distress. However, the clinical course after AEs of IPF (AE-IPFs) has not been well described. Therefore, we aimed to elucidate the clinical course and prognosis in survivors of AE-IPFs., Methods: Consecutive patients with IPF who presented to our institution with their first AE-IPFs between January 2008 and December 2019 were included in this study. Data were retrospectively collected, and the clinical course, survival, and cause of death were further analyzed., Results: Ninety-seven patients were included in this retrospective study. Among them, 67 (69.1%) were discharged alive, with a median survival time after discharge of 1081 days. AE recurrence and pneumonia were the most common causes of death, each accounting for 22.2% of cases among survivors of AE-IPFs. AEs were the most frequent during the first 3 years after discharge, whereas pneumonia was more common thereafter., Conclusions: Survivors of AE-IPFs have a relatively favorable long-term prognosis. Among the survivors of first AE-IPFs, AE recurrence and pneumonia were the most common causes of death after discharge. Therefore, preventing AE recurrence and lung infections is crucial for prolonging survival in survivors of AE-IPFs., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: In the LIBERTY ASTHMA QUEST (ClinicalTrials.gov: NCT02414854) study, dupilumab 200 mg and 300 mg every 2 weeks vs matched-volume placebo reduced severe asthma exacerbations and improved lung function (FEV 1 ), asthma control, and quality of life in patients with uncontrolled, moderate-to-severe asthma (N = 1902). Here, we examine the safety and efficacy of dupilumab in the subpopulation of Japanese patients who participated in QUEST (n = 114; 6%)., Methods: Endpoints assessed were annualized severe exacerbation rates and the effect of treatment over the 52-week treatment period on FEV 1 , asthma control, asthma-related quality of life, and markers of type 2 inflammation., Results: In Japanese patients, dupilumab 200 and 300 mg every 2 weeks vs matched placebo reduced severe asthma exacerbation rates by 44% (P = 0.33) and 75% (P = 0.03), respectively, and improved FEV 1 at Week 12 by 0.20 L (P = 0.05) and 0.17 L (P = 0.12). FEV 1 improvements were rapid (by Week 2) and sustained throughout treatment. Significant and/or numerical improvements vs placebo in asthma control and quality of life were also observed throughout treatment. For each endpoint, greater efficacy was observed in patients with elevated baseline levels of type 2 inflammatory biomarkers (blood eosinophils or FeNO). Dupilumab treatment significantly reduced levels of FeNO and total IgE, but not blood eosinophils., Conclusions: In this subanalysis of QUEST, the efficacy and safety of dupilumab in Japanese patients was comparable to that observed in the overall intention-to-treat population, suggesting no variability in efficacy on the basis of Japanese ethnicity. (Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov number: NCT02414854)., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

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 β 2 -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 β 2 -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., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Pulmonary rehabilitation (PR) is recommended as an effective treatment for patients with chronic obstructive pulmonary disease (COPD). Previous meta-analyses showed that PR improves exercise capacity and health-related quality of life (HRQOL). However, they did not evaluate the effect of PR on the sensation of dyspnea. We searched six databases in May 2019 for randomized controlled trials (RCTs) that examined PR, including supervised lower limb endurance training as a minimal essential component that was continued for 4-12 weeks, in patients with stable COPD, with changes from baseline dyspnea as a primary outcome. Secondary outcomes were changes in exercise capacity, HRQOL, activity of daily life (ADL), physical activity (PA), and adverse events. We calculated the pooled weighted mean difference (MD) using a random effects model. We identified 42 studies with 2150 participants. Compared with the control, PR improved dyspnea, as shown using the British Medical Research Council (MRC) questionnaire (MD, -0.64; 95% CI, -0.99 to -0.30; p = 0.0003), transitional dyspnea index (MD, 1.95; 95% CI, 1.09 to 2.81; p = 0.0001), modified Borg score during exercise (MD, -0.62; 95% CI, -1.10 to -0.14; p = 0.01), and Chronic Respiratory Questionnaire (CRQ) dyspnea score (MD, 0.91; 95% CI, 0.39 to 1.44; p = 0.0007). PR significantly increased exercise capacity measured by the 6 min walking distance time, peak workload, and peak VO 2 . It improved HRQOL measured by the St. George's Respiratory Questionnaire and CRQ, but not on PA or ADL. These results indicated that PR programs including lower limb endurance training improve dyspnea, HRQOL, and exercise capacity in patients with stable COPD., Competing Interests: Conflict of interest Dr. Tohda Y. received lecture fees from Kyorin Pharmaceutical, Co., Ltd. and Teijin Pharma Co., Ltd., and research funding from Kyorin Pharmaceutical Co., Ltd., Meiji Seika Pharma Co., Ltd., Boehringer Ingelheim Co., Ltd., Teijin Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., and Astellas, Pearl Therapeutics, Inc. The other authors report no conflict of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: The severe asthma and severe, uncontrolled asthma (SUA) populations in Japan are not well-studied. We investigated the prevalence of continuously treated severe asthma and SUA patients, their disease burden, and the treatment reality via a Japanese health insurance claims database., Methods: Continuously treated asthma patients (patients prescribed inhaled corticosteroids for asthma ≥4 times in the past year) aged ≥17 years at the index date (latest visit between April 2014 and March 2015 for asthma treatment) were included in this analysis (KEIFU study, UMIN000027695). Asthma severity and control status at the index date were defined using modified criteria of ERS/ATS guidelines. Asthma hospitalization, oral corticosteroid (OCS) use, and total medical expenses were calculated using data up to 12 months post-index date., Results: We identified 10,579 patients as continuously treated asthma patients. Of these, 823 (7.8%) had severe asthma; 267 (2.5%) and 556 (5.3%) patients had SUA and severe, controlled asthma (SCA), respectively. Compared with SCA and mild to moderate asthma patients, a greater percentage of SUA patients required hospitalization (13.7%, 6.2%, and 3.0%, respectively) and were prescribed OCSs (67.4%, 45.9%, and 16.2%, respectively). Yearly total medical expenses were also greater for SUA patients (mean [standard deviation]: 8346 [12,280], vs 5989 [10,483] and 3422 [8800] USD, respectively)., Conclusions: The percentages of severe asthma and SUA patients continuously treated in Japan were obtained through this large-scale analysis using a health insurance claims database. SUA patients had greater medical and economic burdens, suggesting more appropriate treatment is required according to the treatment guidelines., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The comorbidity of asthma and allergic rhinitis is remarkably high, but not much is known about the effects of this combined condition on the quality of life. We aimed to evaluate the factors associated with asthma exacerbations and the effect of the exacerbations on the quality of life (QOL) through a one-year, large-scale, observational study in Japanese patients with asthma and rhinitis., Methods: A case survey by attending physicians and a patient survey was conducted at each assessment timepoint over a period of one year. Patients were divided into two groups according to the presence or absence of asthmatic attacks after enrollment and were matched using propensity scores to evaluate the factors associated with asthma exacerbations and the effect of the exacerbation on QOL., Results: Potential factors associated with asthma exacerbations included high body mass index value, low forced expiratory flow 75% of forced vital capacity (FEF75%), severe rhinitis as determined based on ARIA (Allergic Rhinitis and its Impact on Asthma). Although patients with asthma exacerbations had significantly impaired quality of life at baseline as evidenced by the economic aspects, in addition to physical, mental, and social activities, no further reduction with the attacks was observed., Conclusions: This study suggested that higher body mass index (BMI) and severe asthma as well as severe rhinitis were factors associated with asthma exacerbations. Although patients with asthma exacerbations had impaired QOL, attacks caused no further reduction., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

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: The characteristics and significance of respiratory-related hospitalization in patients with idiopathic pulmonary fibrosis (IPF) in Asian countries remain unknown. The purpose of this study was to define the characteristics of respiratory-related hospitalization and to inspect the relationship between respiratory-related hospitalization and subsequent survival in patients with IPF in Japanese general practice., Methods: Patients with IPF who underwent clinical evaluation between February 2008 and August 2017 were screened. Only those who had undergone evaluation within 1 year after the diagnosis of IPF were included in the study. The post-diagnosis pulmonary function tests were considered the registration point. We then performed a 6-month landmark analysis including only patients who were alive 6 months after the registration. The characteristics of respiratory-related hospitalizations during the 6 months after registration and the association between respiratory-related hospitalization and survival were investigated., Results: A total of 106 patients with IPF were included in the study. The mean forced vital capacity (FVC) at registration was 80.2 ± 25.1% predicted. Seventeen patients (16.0%) had respiratory-related hospitalization during the 6 months after registration. Pneumonia was the most frequent reason for hospitalization (47.0%), followed by acute exacerbation of IPF (29.4%). In multivariate analysis, % predicted FVC (hazard ratio: 0.98, 95% confidence interval: 0.96-0.99, p = 0.004), 6-month decrease in % predicted FVC (1.05, 1.02-1.08, 0.005), and respiratory-related hospitalization (2.45, 1.24-4.85, 0.009) were significantly associated with survival., Conclusions: Pneumonia is the most frequent cause of respiratory-related hospitalization in Japanese IPF patients. Furthermore, respiratory-related hospitalization is significantly associated with subsequent poor survival., (Copyright © 2019. Published by Elsevier B.V.)

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.)

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)., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: In the Phase III CALIMA trial, benralizumab significantly reduced asthma exacerbations, increased lung function, and alleviated symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate the efficacy and safety of benralizumab for Japanese patients in the CALIMA trial., Methods: CALIMA was a randomised, controlled trial of 1306 patients (aged 12-75 years; registered at ClinicalTrials.gov: NCT01914757) with severe asthma uncontrolled by medium- to high-dosage inhaled corticosteroids and long-acting β 2 -agonists (ICS/LABA). Patients received 56 weeks' benralizumab 30 mg either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses Q4W), or placebo Q4W. The primary analysis population was patients receiving high-dosage ICS/LABA with blood eosinophils ≥300 cells/μL. This subgroup analysis covered Japanese patients from this group., Results: Of 83 patients randomised in Japan, 46 were receiving high-dosage ICS/LABA and had blood eosinophils ≥300 cells/μL. Compared with placebo, benralizumab reduced the annual rate of asthma exacerbations by 66% (Q4W; rate ratio 0.34, 95% CI, 0.11-0.99) and 83% (Q8W; rate ratio 0.17, 95% CI, 0.05-0.60); increased prebronchodilator FEV 1 by 0.334 L (Q4W; 95% CI, 0.020-0.647) and 0.198 L (Q8W; 95% CI, -0.118 to 0.514); and decreased total asthma symptom score by 0.17 (Q4W; 95% CI, -0.82 to 0.48) and 0.24 (Q8W; 95% CI, -0.87 to 0.40). Percentages of adverse events were consistent with the overall CALIMA group., Conclusions: Benralizumab reduced annual asthma exacerbations and symptoms, increased lung function, and was well-tolerated by Japanese patients with severe, uncontrolled eosinophilic asthma., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive impairment of lung function and degradation of daily activity; however, this degradation has not been adequately elucidated. The objective of this study was to measure the physical activity of patients with IPF to determine its relationships with physiological parameters and survival rate., Methods: In total, 31 patients with IPF and 20 age-matched healthy participants were enrolled in this study. Physical activity was assessed using a physical activity monitor. The relationships among physical activity, physiological data, questionnaire-based patient-centered data, and survival were examined., Results: Physical activity, expressed as daily activity energy expenditure (AEE), was significantly lower, and the percentage of sedentary time was significantly longer in patients with IPF than in healthy participants. Moreover, AEE was moderately correlated with body-mass index, forced vital capacity, diffusing capacity of carbon monoxide, and partial arterial pressure of oxygen. Relatively strong correlation was also observed between AEE and the 6-min walk distance, but not with daily dyspnea, depression, and health-related quality of life scores. Prognostic analysis indicated that daily AEE was a significant predictor of survival., Conclusions: Patients with IPF were significantly inactive compared with age-matched healthy participants. In patients with more impaired physiological functions, the lower the physical activity was, the more was the sedentary time increased. Furthermore, lower daily physical activity resulted in significantly worse survival., (Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Adult bronchial asthma is characterized by chronic airway inflammation, and presents clinically with variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma induces airway remodeling, leading to intractable asthma. The number of patients with asthma has increased; however, the number of patients who die of asthma has decreased (1.2 per 100,000 patients in 2015). The goal of asthma treatment is to enable patients with asthma to attain normal pulmonary function and lead a normal life, without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management by therapeutic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high levels. Long-acting β 2 -agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonist are recommended as add-on drugs, while anti-immunoglobulin E antibody and oral steroids are considered for the most 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 β 2 -agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by choosing treatment steps for asthma in accordance with the severity of exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-induced asthma, and pregnancy are also important issues that need to be considered in asthma therapy., (Copyright © 2016 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.)

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting β2-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled β2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and cough-variant asthma are also important issues that need to be considered.

Evidence-based medicine (EBM) has generated great interest since the 1990s and many physicians worldwide have based their clinical practice on this idea. Its underlying concepts include a diverse array of findings from clinical epidemiological research. In western countries, many clinical databases of clinical epidemiology are in circulation. Clinical epidemiological research using these data in western countries constitutes the majority worldwide. However, because race, lifestyle, culture, etc., differ among western countries and Japan, it is difficult to apply the results of clinical epidemiological research obtained in Japan to western countries. Unfortunately, there is no large-scale database for respiratory diseases prevalent in Japan. Many specialists agree with the opinion that it is necessary to collect medical information specific to the Japanese population and analyze the clinical data. KiHAC (Kinki Hokuriku Airway Disease Conference) was established in September 2001 with the aim of generating evidence through clinical epidemiological research for airway diseases by targeting physicians practicing respiratory medicine, pediatrics, and otorhinolaryngology, primarily in the Kinki and Hokuriku regions located in the central to western parts of Japan. As a part of the KiHAC, clinical research societies will attempt to cooperate with each other to make joint research possible and to share and utilize information, in addition to further promoting clinical research in the field of respiratory medicine., (Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background and Objective: The effects of ambulatory oxygen for idiopathic pulmonary fibrosis (IPF) patients without resting hypoxemia have not been elucidated. The purpose of this study was to assess the effect of ambulatory oxygen on dyspnea in IPF patients without resting hypoxemia but with desaturation on exertion., Methods: This was a double-blind, placebo-controlled, randomized crossover trial of ambulatory oxygen versus ambulatory air. Patients with IPF who had a partial pressure of arterial oxygen (PaO2) between 60 mm Hg and 80 mm Hg at rest, and desaturation of 88% or less in a room-air 6-min walk test were eligible. Patients underwent a standardized 6-min walk test and a 6-min free walk test under each ambulatory gas. Oxygen and air were provided at 4 L/min intranasally. Dyspnea was evaluated immediately, 1, and 2 min after the tests., Results: Twenty patients (16 men), with a mean age of 73.5 (SD 4.1) years, % predicted forced vital capacity (FVC) of 71.0 (13.3) %, % predicted diffusion capacity for carbon monoxide (DLco) of 57.0 (13.3) %, and PaO2 of 72.5 (5.4) mm Hg were recruited. No significant differences in dyspnea were observed between ambulatory oxygen and air at each time point. However, some patients showed improvement in dyspnea with oxygen on an individual basis., Conclusions: Since oxygen provides no additional benefit over air in terms of exertional dyspnea for IPF patients without resting hypoxemia, routine prescription of ambulatory oxygen is not recommended. However, assessment on an individual basis is necessary. Trial registration. UMIN Clinical Trial Registry; No.:UMIN000005098; URL:http://www.umin.ac.jp/ctr/., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Recent studies show that COPD patients exhibit low-grade systemic inflammation, and that plasma fibrinogen and high neutrophil counts are related to faster declines in lung function. We examined correlations between serum biomarkers and the decline of lung function in COPD patients., Method: Baseline levels of 9 serum biomarkers (TIMP-1, alpha1-antitrypsin, MMP-9, TNF-alpha, TGF-beta, IL-6, IL-8, neutrophil elastase and CRP), fibrinogen and white blood cell counts (WCC) were measured in 96 COPD patients. Lung function was measured at the time of blood sampling and every 3-6 months during the observation period (median 25.0 months)., Results: Twenty patients were rapid decliners of lung function and 53 patients were non-decliners. Neutrophil counts, serum CRP and MMP-9 were significantly higher in the rapid decliners (p<0.05). The annual change of % predicted FEV(1) was inversely correlated with MMP-9 (r=-0.288; p<0.01) and CRP (r=-0.354; p<0.005) (partial correlation coefficients adjusted for age, sex, cardiovascular disease, smoking history, and baseline % predicted FEV(1)). The remaining biomarkers were not correlated with the annual change of % predicted FEV(1)., Conclusion: Serum CRP and MMP-9 levels were related to FEV(1) decline. These markers are good candidates as predictors for rapid decline of FEV(1) in COPD patients. Additional long-term and larger size studies of COPD patients could help determine the exact roles for these biomarkers.

Background: The Asthma Health Questionnaire (AHQ)-Japan is useful for assessing quality of life (QOL) in Japanese patients with asthma. However, no studies have compared the AHQ-Japan to other QOL instruments., Methods: The AHQ-33-Japan and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) were completed simultaneously by 126 Japanese patients with asthma (48 men, 78 women; 58.1 +/- 17.3 years of age), and the data were compared., Results: Poor negative correlations (correlation coefficient (r) = -0.20 to -0.44, P < 0.05) were observed for 38 combinations of the subscales of these QOL instruments. As the severity of the patients' asthma increased, the scores of most subscales of both QOL instruments became worse. However, the AHQ-33 was more sensitive for severity than the SF-36. On logistic regression analysis, high Asthmatic Symptoms, Factors which Worsened Symptoms, Emotion, Daily Activity, and Social Activity subscale scores, as well as a high total 32-item score, of the AHQ-33 were associated with an increased risk of moderate to severe asthma. On the other hand, only the Physical functioning subscale score of the SF-36 was associated with an increased risk of moderate to severe asthma., Conclusions: Our results show that the AHQ-33 is useful as a disease-specific QOL instrument in Japanese patients with asthma and that it is better than the SF-36, which is a generic QOL instrument. In the future, the AHQ-33 should be compared to other asthma-specific questionnaires.

Ten patients with SSPE were surveyed during the last 4 years from the viewpoint of clinical safety for use of ribavirin therapy. Although effectiveness varied among cases, they were all treated safely with intraventricular ribavirin. This study suggests that treatment is safe and well-tolerated.

When five cytotoxicity methods compared the toxicity of eosinophil granule major basic protein (MBP) and melittin to K562 and HL-60 cells, strikingly discrepant results were noted. Trypan blue staining, propidium iodide/CellTrackerGreen staining and incorporation of 14C-leucine assays indicated MBP damages > 75% of cells by 1 h. In contrast, 51Cr and lactic dehydrogenase (LDH) release assays indicated MBP damages most cells only at 20 h. All methods indicated melittin damages nearly all cells by 1 h. Further studies showed that without cell transfer, dye staining methods indicated MBP produces < 10% cytotoxicity after 4 h. A modified 14C-leucine assay, employing sodium dodecyl sulfate solubilization and trichloroacetic acid precipitation, showed lower cytotoxicity, 48%, at 4 h. Modified 51Cr and LDH assays showed increased cytotoxicities at 4 h, 34% and 58%, respectively. Overall, MBP's ability to cause molecular and cellular adhesion systematically confounds standard cytotoxicity measurements. However, the modified 14C-leucine assay provides a valid measure of MBP's cytotoxicity and may be useful for analyses of 'sticky' cytotoxins.