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Rei Fujiki,1 Tomotaka Kawayama,2 Kyoji Furukawa,3 Takashi Kinoshita,2 Kazuko Matsunaga,2 Tomoaki Hoshino2 1Fujiki Medical and Surgical Clinic, Miyazaki, 880-2112, Japan; 2Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, 830-0011, Japan; 3Biostatistics Center, Kurume University School of Medicine, Kurume, 830-0011, JapanCorrespondence: Tomotaka Kawayama, Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan, Tel +81-924-31-7560, Fax +81-942-31-7703, Email kawayama_tomotaka@med.kurume-u.ac.jpPurpose: Few questionnaires evaluate daytime and nighttime symptoms separately, although these assessments could contribute to the improvement of disease control levels and prevention of future risks in asthma. The purpose of this retrospective study was to investigate whether daytime and nighttime visual analog scales (VAS) are useful in measuring the perception of symptoms, assessing disease control levels, and evaluating the treatment effects in asthma.Patients and Methods: Self-reporting asthma control tests (ACT) before and after treatment are standardized tests used to determine disease control levels. A multiple regression analysis was performed to determine the correlation between daytime and nighttime VAS and the characteristics of patients before treatment, as well as the changes in VAS and lung functions and fractional exhaled nitrogen oxide after treatment in 55 treatment-naïve symptomatic adult patients with asthma.Results: Both daytime (r = − 0.57, P < 0.0001) and nighttime (r = − 0.46, P < 0.0001) VAS correlated well with ACT scores, and there was a correlation between daytime and nighttime VAS (r = 0.33, P = 0.0148) before treatment. In addition, the changes in daytime (r = − 0.65, P < 0.0001) and nighttime (r = − 0.44, P < 0.0001) VAS were significantly associated with changes in the ACT scores. The multiple regression analysis (β [95% confidence interval]) revealed that improvements in the daytime (− 2.33 [− 4.55 to − 0.11], P = 0.0405) and nighttime (− 3.09 [− 6.25 to 0.07], P = 0.0505) VAS were associated with an increased forced vital capacity after treatment, although there was no correlation between the VAS and characteristics before treatment.Conclusion: Our study demonstrated that daytime and nighttime VAS were useful in assessing disease control levels and evaluating the treatment effects in asthma.Keywords: asthma, symptoms, visual analog scale, asthma control test, adult

Shingo Tsuneyoshi,1 Tomotaka Kawayama,1 Jun Sasaki,1 Takashi Kinoshita,1 Chiyo Yano,1 Yoshihisa Tokunaga,1 Masanobu Matsuoka,1 Haruki Imaoka,1 Kazuko Matsunaga,1 Kyoji Furukawa,2 Tomoaki Hoshino1 1Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; 2Biostatistics Center, Kurume University School of Medicine, Kurume, JapanCorrespondence: Tomotaka Kawayama, Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan, Email kawayama_tomotaka@med.kurume-u.ac.jpPurpose: Although childhood asthma is a risk factor for adult lung function disorders, the correlation between childhood asthma control level and lung function growth remains unclear in Japan. The correlation between childhood asthma control and early adulthood lung function growth was investigated in this study.Patients and Methods: We included 505 children with asthma from the Omuta City Air Pollution-Related Health Damage Cohort Program. The characteristics and lung function of girls and boys aged 6– 11 years and 12– 17 years were compared between poor and good asthma control groups.Results: Among the 505 children, 214 (42.4%) showed poor asthma control. The mean percentage forced expiratory volume in 1 second predicted for girls and boys aged 6– 11 years (80.2% and 79.2%, respectively) and 12– 17 years (80.0% and 81.1%, respectively) in the poor control group was significantly lower than those of girls and boys aged 6– 11 years (87.9% and 87.3%, respectively) and 12– 17 years (88.1% and 87.8%, respectively) in the good control group. However, a linear regression model did not reveal between-group differences in the slopes of lung function growth for both sexes. Girls (24.6%, P < 0.0001) and boys (24.4%, P = 0.0026) in the poor control group had a significantly higher proportion of young adults with obstructive ventilatory patterns than girls (1.4%) and boys (8.1%) in the good control group.Conclusion: Our findings revealed that poor childhood asthma control leaded to lung function disorders, which suggest the importance of early asthma control in school children.Keywords: childhood asthma, airflow limitation, Japanese, transition, school-age children

Despite the growing population of long-term survivors with human immunodeficiency virus 1 (HIV) exhibiting asthma-like features worldwide, the pathogenesis underlying airway hyperresponsiveness (AHR) and airway inflammation remains unclear. We aimed to investigate AHR and airway inflammation in an HIV-infected Japanese population.Of 94 Japanese participants, 10 HIV-infected participants with asthma were excluded from the study. We compared the characteristics of HIV-infected (n = 34) and non-HIV-infected participants (n = 50). Eosinophilic, neutrophilic, mixed (eosinophilic and neutrophilic), and paucigranulocytic airway inflammatory phenotypes were classified based on induced sputum characteristics.The prevalence of AHR in HIV-infected participants (32.4%) was significantly higher than that in their non-HIV-infected counterparts (10.0%) (P = 0.0213). The multivariate nominal logistic regression analysis revealed HIV as an independent risk factor for AHR. HIV-infected participants were significantly more likely to have a neutrophilic airway inflammatory phenotype than non-HIV-infected participants (P = 0.0358). Furthermore, HIV-infected participants with AHR demonstrated a significant correlation between AHR levels and the percentage of sputum neutrophils (r = -0.65, P = 0.0316). The percentage of sputum neutrophils was negatively associated with the blood CD4 cell count (r = -0.66, P = 0.0266).We observed the high prevalence of AHR and neutrophilic airway inflammatory phenotype in Japanese participants with stable HIV infection. Our findings provide insight into the mechanisms of AHR and may facilitate the development of novel treatment for individuals with AHR and HIV infection.

Background In symptomatic COPD patients with a history of exacerbations, additional treatment with inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy is recommended based on the evidence of low incidence of exacerbations but with a caution for pneumonia. However, ethnic differences may affect the response to drugs. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this treatment in the Japanese population (PROSPERO: CRD42020191978). Methods We searched relevant randomized control trials and analyzed the exacerbations, quality of life, lung function, and adverse events including pneumonia and mortality as the outcomes of interest. Results We identified a total of three RCTs (N = 632). Treatment with ICS/LAMA/LABA triple therapy significantly decreased the exacerbations (rate ratio, 0.56; 95% CI, 0.38 to 0.85) and improved the trough FEV1 (mean difference, 0.04; 95% CI, 0.01 to 0.07) compared to LAMA/LABA therapy. However, triple therapy showed a significantly higher incidence of pneumonia compared to LAMA/LABA (odds ratio, 3.38; 95% CI, 1.58 to 7.22). Concerning other adverse events including mortality, there were no significant difference between these therapies. Conclusions In the current meta-analysis of the Japanese population, we confirmed that triple therapy causes a higher incidence of pneumonia than LAMA/LABA treatment but is a more preferable treatment since it showed a lower incidence of exacerbations and higher trough FEV1 in patients with symptomatic moderate to severe COPD. However, since the sample sizes were not statistically large enough, further trials involving Japanese patients are needed.

Rei Fujiki,1,2 Tomotaka Kawayama,2 Kyoji Furukawa,3 Takashi Kinoshita,2 Kazuko Matsunaga,2 Tomoaki Hoshino2 1Fujiki Medical and Surgical Clinic, Miyazaki, Japan; 2Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan; 3Biostatistics Center, Kurume University School of Medicine, Kurume, JapanCorrespondence: Tomotaka Kawayama, Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan, Tel +81-0942-31-7560, Email kawayama_tomotaka@med.kurume-u.ac.jpPurpose: The efficacy and safety of first-line triple and dual therapy remain unclear because the stepwise strategy is a worldwide standard in controller-naïve asthma. A preliminary retrospective cohort study was conducted to investigate the efficacy and safety of first-line triple and dual therapy for managing controller-naïve and symptomatic adult patients with asthma.Patients and Methods: Patients with asthma who received first-line single-inhaler triple therapy (SITT) or dual therapy (SIDT) for at least 8 weeks were selected between December 1, 2020, and May 31, 2021, in Fujiki Medical and Surgical Clinic, Miyazaki, Japan. Data on daytime and nighttime visual analog scale (VAS) scores, lung function tests, fractional exhaled nitrogen oxide (FENO), and adverse events were compared between SITT and SIDT pre- and post-treatment.Results: The SITT significantly improved the nighttime, but not daytime, VAS scores better than the SIDT 2 weeks post-treatment (P = 0.0026), whereas SITT and SIDT significantly improved daytime and nighttime VAS scores after treatment compared to baseline. Both therapies also significantly improved lung functions and FENO post-treatment. The proportion of patients achieving complete control in the nighttime VAS scores after SITT was significantly higher than that four (P = 0.0186) and 8 weeks (P = 0.0061) after SIDT. Only patients with SITT experienced dry mouth.Conclusion: Our study demonstrated that first-line SITT and SIDT were effective, and SITT improved disease control faster than SIDT in controller-naïve and symptomatic adult patients with asthma. The first-line SITT may contribute to faster and better control levels in symptomatic patients with asthma.Keywords: adult, asthma, cohort study, corticosteroids, Japanese

Journal of Clinical Medicine 11(22), 6623 (2022). doi:10.3390/jcm11226623 special issue: "Topical Collection "Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions" / Collection Editor: Kazuto Matsunaga, Guest Editor", Published by MDPI, Basel

An 82-year-old woman complained of recurring cough and shortness of breath and was diagnosed with progressive multiple myeloma (MM). Chest computed tomography (CT) revealed bilateral ground-glass opacity and interlobular septal thickening predominantly in the lower lung zones. Histopathologic findings obtained by a transbronchial lung cryobiopsy (TBLC) revealed alveolitis and granulomas consistent with granulomatous-lymphocytic interstitial lung disease (GLILD). Aggressive chemotherapy for MM contributed to the improvement in respiratory symptoms and abnormal chest CT findings. In cases of MM with lung abnormalities, the possibility of GLILD must be ruled out, and a TBLC should be considered to attain an accurate diagnosis.

Background Comparative effects on physical activity of mono and dual bronchodilators remain unclear in patients with treatment-naive chronic obstructive pulmonary disease (COPD). We sought to compare the changes in physical activity before and after tiotropium and tiotropium/olodaterol treatment in treatment-naive COPD patients. Methods A prospective, multicenter, randomized, open-labeled, and parallel interventional study was conducted. Eighty Japanese patients with treatment-naive COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks. Spirometry and dyspnea index were assessed, and COPD assessment test (CAT) and the 6-minute walk distance (6MWD) were conducted before and after treatment. Evaluation of physical activity was assessed by a triaxle accelerometer over a 2-week period before and after treatment. Results There were no differences in the mean age (69.8 vs 70.4 years), body mass index (BMI) (22.5 vs 22.6 kg/m2) and mean % forced expiratory volume in 1 second (%FEV1) at baseline (61.5 vs 62.6%) between the two groups. Changes in FEV1 (mean±standard error, 242.8±28.8 mL) and transient dyspnea index (TDI) (2.4±0.3 points) before and after tiotropium/olodaterol treatment were greater than with tiotropium treatment (104.1±31.9 mL, p

We retrospectively analyzed the clinical and laboratory data of patients diagnosed with anti-transcriptional intermediary factor 1 (TIF-1γ) antibody-positive polymyositis (PM)/dermatomyositis (DM) to clarify the characteristics of this disease. We identified 14 patients with TIF-1γ antibody-positive DM (TIF-1γ DM), 47 with anti-aminoacyl-tRNA synthetase antibody (ARS)-positive PM/DM, and 24 with anti-melanoma differentiation-associated gene 5 antibody (MDA-5)-positive PM/DM treated at the Kurume University Hospital between 2002 and 2020. Patients with TIF-1γ DM were significantly older than the other two groups. Nine patients with TIF-1γ DM were female, thirteen patients had DM, and one had clinically amyopathic DM. Primary malignant lesions were lung (3), uterus (2), colon (2), breast (2), ovary (1), lymphoma (1), and unknown (2). Cutaneous manifestation and dysphagia were the most common symptoms in TIF-1γ DM. Erythema (9/14), the V-neck sign (8/14), heliotrope (9/14), and nailfold telangiectasia (14/14) were significantly more common in TIF-1γ DM. Furthermore, no patients with TIF-1γ DM had interstitial lung abnormality on high-resolution CT. In patients with TIF-1γ DM, the frequency of dysphagia and unusual erythema, particularly that which spreads from the trunk, and nailfold telangiectasia, were characteristic findings. In most patients with TIF-1γ DM, it is necessary to administer other immunosuppressive drugs along with glucocorticoids.

Background The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) is not adequately studied. Methods We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of a short-acting muscarinic antagonist (SAMA) therapy combined with a long-acting beta-2 agonist (LABA) in patients with stable COPD. Pulmonary function, dyspnea, health-related quality of life, exercise tolerance, physical activity, exacerbations of COPD, and adverse events during regular use were set as outcomes of interest. Results We included five controlled trials including two sets of publicly available online data without article publications for the meta-analysis. Additional use of SAMA plus LABA showed a significant improvement in the peak response in FEV1 (mean difference (MD) 98.70 mL, p < .00001), transitional dyspnea index score (MD .85, p = .02), and St George’s Respiratory Questionnaire score (MD -2.00, p = .008) compared to LABA treatment. There was no significant difference in the risk of exacerbation of COPD ( p = .20) and only a slight trend of increased severe adverse events (OR: 2.16, p = .08) and cardiovascular events (OR: 2.38, p = .06). Conclusion Additional treatment with SAMA combined with LABA could be a feasible choice due to its efficacy and safety.

Background: The long-term prognosis of asthma with airflow obstruction is poorly understood in Japan. The aim of this retrospective 26-year study was to investigate the long-term mortality risk of airflow obstruction in asthmatics. Methods: Using data from the Omuta City Air Pollution-related Health Damage Cohort Program, mortality risk ratios of airflow obstruction in Japanese Individuals were analyzed by Cox proportional hazards models. Airflow obstruction was considered to be present when the forced expiratory volume in 1 sec (FEV1)/forced vital capacity ratio was

Kentaro Machida,1,* Tomotaka Kawayama,2,* Masaharu Kinoshita,3,* Masakazu Ichinose,4 Tohru Tsuda,5 Shohei Takata,6 Hiroshi Koto,7 Makoto Yoshida,8 Yoshinori Ashihara,9 Masaru Kawashima,10 Hideaki Suna,10 Hiromasa Inoue1 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; 2Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan; 3Nagata Hospital, Yanagawa 832-0059, Japan; 4Department of Respiratory Medicine, Tohoku University, Graduate School of Medicine, Sendai 980-8574, Japan; 5Kirigaoka Tsuda Hospital, Kitakyushu 802-0052 Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka-Higashi Medical Center, Koga 811-3195, Japan; 7Division of Respiratory Medicine, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka 815-8588, Japan; 8Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka 811-1394, Japan; 9Division of Respiratory Medicine, Oita Nakamura Hospital, Oita 870-0022, Japan; 10ONO Pharmaceutical Co. Ltd., Osaka 541-8564, Japan*These authors contributed equally to this workCorrespondence: Hiromasa InoueDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, JapanTel +81 99 275 6481Fax +81 99 275 6482Email inoue-pulm@umin.netBackground: Although long-acting muscarinic receptor antagonists are central to the management of chronic obstructive pulmonary disease (COPD), inhaled medicines may have technical difficulty in some patients and adherence barriers.Methods: A multicenter, randomized, double-blind, placebo-controlled 3×3 crossover Phase II trial was performed to evaluate the efficacy and safety of oral administration of the antimuscarinic agent imidafenacin in patients with COPD. Twenty-seven male COPD patients with % forced expiratory volume in 1 s (FEV1) ≥30% and

Koichiro Takahashi,1 Hiroki Tashiro,1 Ryo Tajiri,2 Ayako Takamori,2 Masaru Uchida,3 Go Kato,4 Yuki Kurihara,1 Hironori Sadamatsu,1 Takashi Kinoshita,5 Makoto Yoshida,6 Atsushi Kawaguchi,2,7 Shinya Kimura,1 Naoko Sueoka-Aragane,1 Tomotaka Kawayama5 On behalf of Saga-naïve COPD Physical Activity Evaluation (SCOPE) Study Investigator Group1Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan; 2Clinical Research Center, Saga University Hospital, Faculty of Medicine, Saga University, Saga, Japan; 3Division of Internal Medicine, Japan Community Health Care Organization Saga Central Hospital, Saga, Japan; 4Division of Respiratory Medicine, Saga Prefectural Medical Center Koseikan, Saga, Japan; 5Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan; 6Division of Respiratory Medicine, National Hospital Organization Fukuoka Hospital, Fukuoka, Japan; 7Education and Research Center for Community Medicine, Faculty of Medicine, Saga University, Saga, JapanCorrespondence: Koichiro TakahashiDivision of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, JapanEmail takahak@cc.saga-u.ac.jpBackground: Prolonged sedentary behavior is associated with worse prognosis in patients with chronic obstructive pulmonary disease (COPD). Our previous study found that first-line dual therapy with tiotropium/olodaterol significantly reduces sedentary time compared to tiotropium monotherapy in Japanese patients with treatment-naïve COPD, although the characteristics of responders to dual-therapy versus monotherapy for COPD are still unclear.Methods: Patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks. Physical activity was assessed using a triaxle accelerometer for 2 weeks before and after treatment. This analysis focused on the change in sedentary time, indicated by physical activity of 1.0– 1.5 metabolic equivalents (METs), with stratification for the following factors: age, body mass index (BMI), pulmonary function, COPD assessment test (CAT), the 6-minute walk distance (6MWD), and physical activity level at study entry.Results: Thirty-five patients received tiotropium/olodaterol and 34 patients received tiotropium. In patients with lower inspiratory capacity at study entry, a significant reduction in sedentary time was observed in the tiotropium/olodaterol group compared with the tiotropium group (Tio: − 12.8 ± 13.5 min, Tio/Olo: − 65.1 ± 21.0 min, mean difference, − 52.2 min, 95% CI − 103.6 to 0.88, p = 0.046). In patients with a shorter duration of physical activity of ≥ 2 METs at study entry, a significant reduction of sedentary time was observed in the tiotropium/olodaterol group compared with the tiotropium group (Tio: − 3.3 ± 17.5 min, Tio/Olo: − 72.9 ± 23.1 min, mean difference, − 69.7 min, 95% CI − 128.7 to − 10.6, p = 0.02). There were no differences in terms of age, BMI, CAT score, 6MWD, FEV1, FVC, VC, and physical activity of 1.0– 1.5 METs and ≥ 3.0 METs.Conclusion: This study showed that COPD patients with lower inspiratory capacity or shorter active time of ≥ 2.0 METs at study entry are likely to exhibit significantly greater reduction in sedentary time with tiotropium/olodaterol treatment.Keywords: chronic obstructive pulmonary disease, physical activity, sedentary time, long-acting muscarinic antagonist, long-acting beta 2 agonist

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced >= 1 exacerbation in the previous 12 months, of whom 72.3% experienced >= 1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation +/- 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score = 2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring >= 1 emergency department visit and 1.1% requiring >= 1 hospital admission. Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

Background: Bronchodilators improve lung function, QOL and exercise tolerance in patients with COPD, however effects of bronchodilators in physical activity (PA) are still unclear. We investigated the effects of an introduction of bronchodilators on pulmonary function, dyspnea, QOL and PA in patients with treatment-naive COPD. Methods: This is a prospective, multicenter, randomized interventional study included 80 treatment-naive COPD subjects who were randomized to receive either tiotropium (Tio) or tiotropium/olodaterol (Tio/Olo) treatment for 12 weeks. The subjects were examined by pulmonary function tests, BDI/TDI, COPD assessment tests and PA measured using a triaxle accelerometer before and after treatment. Results: The differences in FEV1.0 after administration of the bronchodilator for 12 weeks were 242.8±28.8 ml for Tio/Olo vs. 104.1±31.9 mL for Tio (p Conclusion: These data suggest that Tio/Olo improves not only pulmonary function, but also reduces the time in the sedentary position in patients with treatment-naive COPD.

We present a pulmonary sarcoidosis patient with specific elevation of serum Krebs von den lungen-6 (KL-6) levels, who was successfully treated with inhaled corticosteroids. Pulmonary sarcoidosis was initially identified as a chest radiograph abnormality during a routine medical examination, and subsequently confirmed by a high serum level of soluble interleukin 2 receptor. The patient was started on high-dose inhaled budesonide because of high serum levels of angiotensin-converting enzyme (ACE) and KL-6. Following treatment, radiographic findings improved, ACE levels normalized, and serum KL-6 levels markedly decreased. No recurrence was detected at 100 months with a budesonide dosage of 800 μg/day. This case demonstrates the efficacy of highdose inhaled corticosteroids for the initial treatment of pulmonary sarcoidosis.

A 78-year-old man who had worked in the building industry visited our hospital because of groundglass opacity with smoothly thickened, intralobular interstitial lines and interlobular septal lines on chest high-resolution computed tomography (HRCT). HRCT image also showed a focal area of reticulation and pleural thickening. Lung specimens obtained by surgical lung biopsy showed accumulations of intra-alveolar periodic acid-Schiffpositive materials, usual interstitial pneumonia (UIP)-like subpleural lung fibrosis and asbestos bodies (1 body/cm2 in high-power field, ×400). Serum granulocyte-macrophage colony stimulating factor autoantibody was positive. The patient was diagnosed as having autoimmune pulmonary alveolar proteinosis (PAP) and needed differential diagnosis from secondary PAP caused from pulmonary asbestosis and UIP. Careful observation of the manifestations of pulmonary asbestosis and the progression of fibrosis using HRCT will be necessary in this patient.

A 56-year-old healthy man who was a current smoker died from fulminant tracheobronchial aspergillosis despite a month of treatment with a combination of intravenous anti-fungal agents that had been started immediately after the diagnosis. This case report is important for understanding and managing fulminant Aspergillus infections in healthy subjects, although the pathogenesis and underlying pathways are still unknown.

Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab) is associated with fatal rapidly progressive interstitial lung disease (RP-ILD) in patients with dermatomyositis (DM). We attempted to clarify whether anti-MDA5-Ab is associated with long-term outcomes in patients with DM-ILD.Thirty-six patients with DM-ILD were retrospectively analyzed for their serum anti-MDA5-Ab by using an enzyme-linked immunosorbent assay. We analyzed the association between clinical parameters, including the serum levels of anti-MDA5-Ab and ferritin.Fourteen patients (39%) were positive for anti-MDA5-Ab. The serum levels of anti-MDA5-Ab and ferritin in 7 patients with acute death were higher than those in the surviving patients. An "unclassifiable pattern" on chest computed tomography and the development of RP-ILD were also prognostic markers. The serum levels of anti-MDA5-Ab and ferritin (cut-off levels, 100 IU/mL and 899 ng/mL, respectively) were markers predictive of acute death, showing good sensitivity (86% and 83%) and specificity (97% and 100%). All 7 patients with acute death developed RP-ILD and were positive for anti-MDA5-Ab, including 6 patients with a high titer (≥100 IU/mL), whereas only 2 patients (29%) developed RP-ILD among the 7 survivors with a low titer of anti-MDA5-Ab (100 IU/mL). In contrast, a low positive titer of anti-MDA5-Ab was not associated with changes in pulmonary function for 2 years.Although a high serum titer of anti-MDA5-Ab (≥100 IU/mL) is associated with acute death via the development of RP-ILD, outcomes in the chronic phase for patients with a low titer of anti-MDA5-Ab (100 IU/mL) were similar to those of patients without anti-MDA5-Ab.

OBJECTIVES Relapsing polychondritis (RP) is a very rare autoimmune disorder characterized by recurrent episodes of inflammation and destruction of cartilaginous tissues. We examined the clinical characteristics, management, and outcomes of Japanese RP patients. METHODS We identified 8 RP cases in our department between 2003 and 2017. Detailed clinical features, testing, treatment, and outcomes were recorded. RESULTS The mean time from symptom onset to diagnosis was 9 months. Four cases presented with auricular chondritis and laryngotracheal involvement and 3 cases presented with a saddle nose deformity. Anti-type II collagen antibody was positive in 5 of 6 cases. Of 3 cases with associated diseases (rheumatoid arthritis, ulcerative colitis, and Sjogren's syndrome), 2 died of respiratory failure. CONCLUSIONS When RP is diagnosed, early computed tomography or pulmonary function testing is essential to enable early treatment. Undiagnosed airway involvement can cause tracheobronchial wall fibrosis, leading to fixed stenosis.

BACKGROUND The role of IL-38, a new member of the IL-1 family, in airway eosinophilic inflammatory conditions such as asthma is unclear. To investigate the role of IL-38 in airway eosinophilic inflammation, an IL-38-gene deficient (KO) murine asthma model was analyzed. METHODS The numbers of eosinophils and neutrophils, and levels of IL-5, IL-13 and IL-17A protein and mRNA in bronchoalveolar lavage fluid (BALF) and lung tissue were compared between wild-type (WT) and IL-38-KO mice after OVA sensitization and challenge. The effects of additional purified recombinant mouse (rm) IL-38 protein were investigated in the IL-38-KO murine asthma model. RESULTS The IL-38 and IL-5 mRNA in WT mice was significantly higher after OVA challenge than after saline challenge (p

We describe a case of a woman who presented with a persistent cough, general fatigue, and a fever. Interstitial lung disease was rapidly progressive and resistant to high-dose steroid therapy. She tested positive for the presence of anti-melanoma differentiation-associated gene 5 (MDA-5) antibody, although she had no skin manifestations of dermatomyositis. She was eventually diagnosed with unclassifiable idiopathic interstitial pneumonia and was successfully treated with intensive immunosuppressive therapy including intravenous cyclophosphamide. To our knowledge, this is the first report of anti-MDA-5 antibody in a patient with idiopathic interstitial pneumonia.

Background Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. Methods To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. Results IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. Conclusions IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF.

Background Inhaled bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) play a central role in the treatment of stable chronic obstructive pulmonary disease (COPD). However, it is still unclear whether LABA or LAMA should be used for the initial treatment. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LABA versus LAMA in patients with stable COPD. Methods We searched relevant randomized control trials (RCTs) with a period of treatment of at least 12 weeks and analyzed the exacerbations, quality of life, dyspnea score, lung function and adverse events as the outcomes of interest. Results We carefully excluded unblinded data and identified a total of 19 RCTs (N = 28,211). LAMA significantly decreased the exacerbations compared to LABA (OR 0.85, 95% CI 0.74 to 0.98; P = 0.02). In St George’s Respiratory Questionnaire and transitional dyspnoea index score, there were no differences between LABA and LAMA treatment. Compared to LABA, there was a small but significant increase in the trough FEV1 after LAMA treatment (Mean difference 0.02, 95% CI 0.01 to 0.03, P = 0.0006). In the safety components, there was no difference in the serious adverse events between LABA and LAMA. However, LAMA showed a significantly lower incidence of total adverse events compared to LABA (OR 0.92, 95% CI 0.86 to 0.98; P = 0.02). Conclusion Treatment with LAMA in stable COPD provided a significantly lower incidence of exacerbation and non-serious adverse events, and a higher trough FEV1 compared to LABA. Trial registration (PROSPERO: CRD42019144764)