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Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years; 48 males and 5 females; GOLD 1/2/3/4 = 19/27/6/1; mMRC 0/1/2/3/4 = 14/22/12/4/1; UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.

Objective Benralizumab is a promising drug for severe uncontrolled asthma. This study aimed to clarify the effectiveness of benralizumab in a real-life setting. Methods Subjects included 24 patients with severe type 2 asthma who received benralizumab between April 2018 and July 2019. Changes in parameters, exacerbation frequency, and oral corticosteroid (OCS) use after 4 and 24 weeks of administration were examined. The parameters included the Global Evaluation of Treatment Effectiveness (GETE) scale, Asthma Control Questionnaire (ACQ), Asthma Control Test (ACT), blood eosinophils, fractional exhaled nitric oxide (FeNO), and spirometry. The response to treatment was defined as follows: for patients with exacerbations or OCS use before treatment initiation, a reduction of ≥50% in exacerbation frequency or OCS use; and for patients without exacerbations or OCS use, an improvement of ≥0.5 in ACQ scores and ≥3 in ACT scores, or of ≥10.38% in FEV1. Results Twenty-one patients completed the treatment for 24 weeks. Excellent and good GETE scales and ACQ and ACT improvement were found in 67% of the patients at 4 weeks, and the effect continued until 24 weeks. The patients' rate with exacerbations was significantly reduced compared to the previous 24 weeks before administration. In 17 patients receiving OCS, the use could be reduced or quit in 14 patients. Overall, 16 patients (76.2%) met the responder definition and could be predicted by the baseline eosinophil count and FeNO levels with the best cutoff values of 100/μL and 40 ppb, respectively. Conclusions Blood eosinophil and FeNO could predict benralizumab effectiveness.

Background Cough and sputum are the major symptoms of pulmonary tuberculosis (TB). However, the relationship between these symptoms and treatment for TB is not fully understood. The aim of this prospective study was to clarify the cough- and sputum-related quality of life (QOL) in patients with pulmonary TB before and after initiation of treatment. Methods The study included 85 patients with active pulmonary TB who were hospitalized from July 2014 to August 2015. They completed the Leicester Cough Questionnaire (LCQ: range 3–21, the higher the better) and the Cough and Sputum Assessment Questionnaire (CASA-Q: range 0–100, the higher the better) on admission and at discharge after 2 months of treatment. Results The LCQ and CASA-Q scores were reduced on admission. A multivariate linear regression analysis revealed that younger age, more than two cavitary lesions, and the presence of bronchial TB were associated with reduced LCQ total score. However, each score significantly improved at discharge, regardless of the initial grade of the sputum smear, site of the lesion, number of cavitary lesions, and presence of bronchial TB. The change in the mean LCQ total score was 2.28 (95% confidence interval, 1.56–3.00). The changes in the mean CASA-Q cough symptoms, cough impact, sputum symptoms, and sputum impact scores were 22.84 (18.44–27.25), 10.96 (7.20–14.71), 17.25 (13.33–21.18), and 5.25 (2.49–8.00), respectively. Conclusions Cough- and sputum-related QOL was impaired in patients with pulmonary TB before treatment but improved after initiation of treatment regardless of the clinical characteristics.

Background: There are no standard cytotoxic treatments for non-small-cell lung cancer (NSCLC) patients beyond third-line therapy. The purpose of this study was to evaluate the efficacy and safety of amrubicin in pretreated NSCLC patients. Methods: The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at Shizuoka General Hospital between April 2007 and March 2015 were retrospectively reviewed. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Results: Overall, 69 patients were enrolled in this study; 16 patients were female and the median age was 67 years. The median number of treatment cycles was 3. The response rate was 7.2%, and the disease control rate was 63.8%. The median progression-free survival was 2.8 months. The median overall survival was 7.7 months. Hematological toxicities of ≥ grade 3 included leukopenia (59.4%) and neutropenia (62.3%). Non-hematological toxicities of ≥ grade 2 included anorexia (27.5%) and fatigue (24.6%). Conclusion: Although hematological toxicities were severe, these results suggested that amrubicin in NSCLC patients beyond third-line therapy shows sufficient clinical benefit.

Background The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial. Methods To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case–control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department. Results There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12). Conclusion This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.

Subacute invasive pulmonary aspergillosis (SIPA), a rapidly progressive fungal infection of less than three months arising from pre‐existing lung lesions, generally afflicts moderately immunocompromised patients. We herein report the case of a 69‐year‐old man who developed SIPA following chemoradiotherapy for lung cancer and treated with antifungal therapy. He presented with fever, and computed tomography revealed a cavity with surrounding consolidation. The cavity itself had been considered as the primary tumour treated by chemoradiotherapy. Bronchoalveolar lavage by bronchoscopy performed at admission identified Aspergillus fumigatus; no other pathogens or malignant cells were observed. Owing to the worsening of symptoms and inflammation despite micafungin administration, the treatment was changed to liposomal amphotericin B with voriconazole, which led to clinical improvement. In addition to cancer recurrence and bacterial infection, fungal infection should also be considered in patients undergoing chemoradiotherapy for lung cancer with deteriorating imaging findings and symptoms. In intractable cases, multiple antifungal drugs are effective., Subacute invasive pulmonary aspergillosis (SIPA), a rapidly progressive fungal infection of less than three months arising from pre‐existing lung lesions, generally afflicts moderately immunocompromised patients. We herein report the case of a 69‐year‐old man who developed SIPA following chemoradiotherapy for lung cancer and treated with multiple antifungal therapy.

The usefulness of the oscillometry, known as forced oscillation technique, for predicting exercise tolerance in subjects with COPD is unknown. To test the hypothesis, we investigated whether oscillometry could predict a 6-minute walking distance (6MWD) 1, 61.0%). Modified MRC dyspnea scale (mMRC), COPD Assessment Test (CAT), oscillometry, spirometry, and 6MWT were performed in a stable condition. The participants were classified into subjects with 6MWD ≥350 m or 6MWD 1, IC, 6MWD, lowest SpO2, maximum Borg scale, respiratory resistance (Rrs), and reactance (Xrs). In multivariate regression analysis, a 6MWD 20/L/s. In conclusion, the oscillatory parameter, inspiratory R5, predicted low exercise tolerance in COPD subjects.

Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p < 0.006). However, there were no changes in mMRC scores, spirometric indices, or forced oscillation parameters. Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.

Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. The negative expiratory pressure (NEP) technique has been the gold standard to detect EFL, while the forced oscillation technique (FOT) has also been reported to detect it. However, the association of FOT with NEP is not fully understood. We assessed whether broadband frequency FOT would predict the presence of EFL measured by NEP. FOT, NEP, and spirometry were performed in 51 patients with COPD. The extent of emphysema was measured by high-resolution computed tomography and scored. Fifteen patients were classified into the EFL-positive group and 36 into the EFL-negative group. In multivariate logistic regression analysis, EFL was independently predicted by emphysema score, forced vital capacity, and whole-breath respiratory system reactance at 5Hz (X5). The receiver operator characteristic curve analysis revealed that inspiratory X5 best predicted EFL-positivity. X5-related forced oscillatory parameters are useful for detecting EFL in the management of COPD.

Reports of chronic eosinophilic pneumonia (CEP) after radiation therapy are limited to breast cancer. We herein describe a case of CEP after radiation therapy for lung cancer. The patient was a 65-year-old man who had asymptomatic peripheral blood eosinophilia but no history of asthma or allergy. One month after completion of radiation therapy, chest CT scan revealed infiltrates inside the irradiated area, leading to the diagnosis of radiation pneumonitis. His condition improved after receiving corticosteroids. However, one months after withdrawal of corticosteroids, he noticed cough and shortness of breath with patchy ground glass opacity in the contralateral lung. The WBC count was 9900/μl with 17% eosinophils and bronchoalveolar lavage showed eosinophils of 14%, leading to the diagnosis of CEP. His condition improved after receiving corticosteroids and subsequent tapering without recurrence. Asymptomatic peripheral blood eosinophilia at the initial diagnosis of lung cancer might be a trigger for developing CEP.

Background: The usefulness of the forced oscillation technique (FOT) in diagnosing cough variant asthma (CVA) has not been demonstrated. Aims: This retrospective study aimed to evaluate diagnostic accuracy of the changes in respiratory system resistance (Rrs) and reactance (Xrs) as possible predictors of CVA. Methods: Twenty-six patients with CVA and 20 with non-CVA (gastroesophageal reflux disease, rhinosinusitis, and post-infectious cough) were enrolled. FOT (MostGraph-01) and spirometry were performed in airway reversibility testing. Fractional exhaled nitric oxide (FeNO) was also measured before the testing. A diagnosis of CVA was based on an isolated cough lasting for at least 8 weeks without wheezing, which was relieved by β2 agonists. Receiver operator characteristic (ROC) curves were constructed to assess which parameters would predict CVA diagnosis. Results: CVA patients showed a significant improvement in Rrs at 5 Hz (R5), Xrs at 5 Hz (X5), resonant frequency (Fres), and a low-frequency reactance area (AX), but not in spirometric indices. ROC curve analyses revealed that the changes in R5, X5, Fres, and AX were superior to the change in FEV1 or the FeNO value to diagnose CVA. The best area under the curve was 0.72 for AX with the optimal cutoff point of 0.41 cmH2O/L (sensitivity, 0.98; and specificity, 0.62). Conclusion: The FOT is superior to spirometry or FeNO measurements in predicting CVA.

Introduction: There are few published reports regarding the clinical benefits of pneumococcal vaccination for the prevention of pneumococcal pneumonia among elderly outpatients with chronic respiratory diseases. Objectives: To evaluate the effectiveness of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a 13-valent pneumococcal conjugate vaccine (PCV13) among elderly outpatients. Methods: This report describes a case-control study including 4124 outpatients aged ≥65 years with chronic respiratory diseases, treated from 2015 to 2017 in our department. Study outcomes were pneumococcal pneumonia incidence rates in the PPSV23 group, the PCV13 group and the non-vaccination group. The effect of each vaccination within 5 years was evaluated as an odds ratio (OR) adjusted by a propensity score, which was predicted using age, gender, comorbidities, and steroid use. ORs and 95% confidence intervals (CIs) of vaccination were calculated using a logistic regression model. Results: There were 377 vaccinated patients (PPSV23, 327 and PCV13, 50), and 143 were diagnosed with pneumococcal pneumonia (Table). Conclusions: There were no significant differences between the vaccination group and the non-vaccination group, possibly because of the differences in background factors and physicians’ recmmendations.

Chronic obstructive pulmonary disease (COPD) is an underdiagnosed lung disease in Japan and worldwide. A nationwide survey in Japan estimated the prevalence to be at least 8.6% (5 million patients) [1]. However, it has been reported that only 220,000 patients are receiving treatment [2]. We hypothesized that some patients hospitalized with pneumonia would have undiagnosed COPD. In this prospective observational single-center study, we clarified the prevalence and clinical features of undiagnosed COPD in hospitalized patients diagnosed with pneumonia.

Introduction: A treatment strategy for COPD patients with eosinophilic airway inflammation has not yet been established. Objective: To examine the effects of an add-on treatment with budesonide/formoterol (BUD/FM) combination in COPD patients with eosinophilic airway inflammation. Methods: Subjects included 83 patients with COPD receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. This was a prospective, single center, open-label, uncontrolled longitudinal study. After an 8-week run-in period, patients underwent measurements of fractional exhaled nitric oxide (FeNO); patients with FeNO levels of >35 ppb were eligible for this study. BUD/FM was used as an add-on therapy in patients receiving LAMA. In patients receiving LAMA/LABA, BUD/FM was added after discontinuation of LABA. Study outcomes included mMRC, CAT, spirometric indices, forced oscillation parameters, and FeNO after 8 weeks of BUD/FM add-on treatment. Results: Of the 83 patients assessed for eligibility, 18 patients (21.7%) had FeNO levels of >35 ppb, and 16 patients completed the study (median age: 74 years). The median CAT score significantly improved (5 to 4, p = 0.032) and nine patients (56.0%) showed >2 points improvement. The median FeNO levels significantly decreased from 52.5 to 35.0 ppb (p Conclusions: Add-on treatment with BUD/FM improves symptoms in COPD patients with eosinophilic airway inflammation. Data are expressed as the median.

Introduction: The 6-minute walk distance (6MWD) in the 6-minute walk test (6MWT) has been used to examine subjective dyspnea and clinical outcomes and predict mortality in patients with COPD. Aims and objectives: We hypothesized that the total step count (TSC) during the 6MWT would be a more useful index than the 6MWD. In this prospective observational study, we assessed the utility of the TSC in patients with mild to moderate COPD. Methods: Subjects included 59 outpatients with COPD (56 males and 3 females; median age: 72 (49-82) years; %FEV1, 64.4%). Spirometry and the 6MWT were performed while the subjects were in a stable condition. A 3-axis accelerometer (Anypal Walk, FUKUDA DENSHI Co. Ltd., Tokyo, Japan) was used to measure the 6MWD, TSC, and the number of steps per second (NSPS). Results: The mean values of the examined parameters were as follows: 6MWD, 407.8 m; TSC, 618.3 steps; and NSPS, 1.78 steps/sec. Significant correlations were detected between the TSC and the lowest oxygen saturation value obtained by pulse oximetry (SpO 2 ), max Borg scale, modified Medical Research Council (MRC) scale, and %FEV1(Table1). NSPS was also correlated with the lowest SpO 2 value, max Borg scale, modified MRC scale, and the %FEV1. The 6MWD was correlated with the max Borg scale, modified MRC scale, and %FEV1, but not with the lowest SpO 2 value. Conclusions: TSC is more useful than the 6MWD for evaluating dyspnea and oxygen desaturation during the 6MWT.

Introduction: Airway hyper-responsiveness (AHR) is a cardinal feature of asthma. In a continuous methacholine challenge test (MCT) using Astograph (Chest, Tokyo, Japan), AHR is measured by the methacholine respiratory system resistance dose-response curve. However, information regarding the relationship between AHR and the broadband frequency forced oscillation technique (FOT) is limited. Aims and objective: To investigate the relationship between AHR and the FOT parameters. Methods: Subjects included 37 patients with asthma. AHR and FOT parameters were measured with Astograph and MostGraph (Chest, Tokyo, Japan), respectively. FOT, spirometry, and fractional exhaled nitric oxide (FeNO) were performed before MCT. We used the value of the cumulative dose of inhaled methacholine measured at the inflection point at which respiratory conductance starts to decrease (Dmin) as an index of AHR. This variable was measured in terms of a unit defined as a 1-minute inhalation of methacholine (1 mg/ml). We defined Dmin less than 10 units as AHR. Results: Dmin correlated with inspiratory respiratory system resistance at 5 Hz (R5), 20 Hz (R20), low-frequency area (ALX) and FeNO before MCT (r=-0.495, -0.489, -0.367 and -0.383, respectively). An ROC curve analysis to identify AHR revealed that the area under the curve of R5 (0.741) was larger than those of other parameters. Conclusions: R5, a forced oscillatory parameter, before MCT predicts AHR.

The usefulness of the forced oscillation technique (FOT) for predicting the treatment outcomes in untreated asthmatic patients is unknown. We investigated whether FOT could predict an improvement in FEV1 following treatment. FOT, spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients before and after undergoing a minimum of two months combination therapy of inhaled corticosteroids and long-acting β2-agonists. The patients were classified as responders or nonresponders to treatment based on the presence or absence of a 10% improvement in the FEV1. The responders to the treatment regimen exhibited lower FEV1, FEV1/FVC, FEF25-75%, and higher respiratory resistance at 5Hz (R5), as well as a difference between R5 and R20 (R5-R20) at baseline compared to the nonresponders. In the multivariate logistic regression analyses, a change in FEV1 greater than 10% was independently predicted by the R5 (adjusted odds ratio: 15.9). The ROC curve analyses revealed that the area under the curve for R5 (0.731) was larger than that of the other parameters. Thus, R5 is a forced oscillatory parameter and predicts an improvement in FEV1 following treatment.

背景．経気管支肺生検で診断し，マクログロブリン血症を呈したMALTリンパ腫の1例を報告する．症例．症例は68歳男性．入院7年前に会社の健診で胸部異常影を指摘され，近医へ通院していたが，著変ないため1年で自己中断した．入院3か月前より労作時呼吸困難，入院1か月前より咳・痰を自覚し，当科外来を受診．低酸素血症および胸部X線写真上，右胸水貯留，両側浸潤影を認め，同日入院となった．末梢血および胸水中に形質細胞様に分化した異型なリンパ球を多数認めた．気管支鏡検査を施行し，肺の生検組織でt（11；18）（q21；q21）の染色体異常を認め，MALTリンパ腫と診断した．血漿交換および化学療法を施行し，治療効果を認めた．結論．MALTリンパ腫は消化管に発症することが多いが，時に，緩徐進行性に肺に発症し，さらに，マクログロブリン血症を呈することは稀である．

今回われわれは, がん性腹膜炎による出血性貧血を併発した症候性むずむず脚症候群に対して, 輸血が有効であったがん終末期症例を経験した. 症例は, 70歳代, 女性, 肝細胞がん. 下肢の異常感覚に対して, 赤血球輸血の施行後に症状の劇的な改善を認めた. がん終末期では, 症候性むずむず脚症候群を合併する頻度は高いと予想され, 積極的な診断と適切な治療が必要であると考えられた. Palliat Care Res 2011; 6(2): 344-349

Classically, metastatic tumours are solid, multiple, well-circumscribed, and rarely cavitary. This rare case of metastatic pulmonary malignant melanoma showed a ring-shaped ground-glass opacity and then the halo sign, depending on the disease progression.

Asthma exacerbation is associated with respiratory infections, including those by viruses and atypical bacteria. We herein report a case of severe acute asthma in an adult caused by Chlamydophila pneumoniae (C. pneumoniae) infection. A 39-year-old woman without a history of asthma reported to the emergency department with progressive worsening of cough, shortness of breath, and wheezing with low oxygen saturation. A computed tomography (CT) scan revealed patchy ground-glass opacity and bronchial wall thickening. She was treated with systemic corticosteroids, inhaled short-acting β2 agonists, aminophylline, doripenem, and levofloxacin. Through successful treatment in the intensive care unit (ICU), her condition and the chest X-ray and CT findings improved. Chlamydophila pneumoniae infection was confirmed by elevated paired serum C. pneumoniae-specific IgA antibodies. Chlamydophila pneumoniae infection is an important cause of severe acute asthma. On CT, findings typical of C. pneumoniae pneumonia were noted.

Respiratory system reactance changed over 5 years and the initial level predicted the rate of change in COPD patients http://ow.ly/ONzz308E3aD

We herein report the clinical and laboratory characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis (PM/DM). We compared these characteristics with previously published findings. Previous reports and our present cases show that anti-OJ autoantibody-positive interstitial lung disease (ILD) patients with PM/DM lack the manifestations of Raynaud's phenomenon and sclerodactyly and show good prognoses and responses to glucocorticoid therapy. These results indicate that the presence of anti-OJ autoantibodies may be useful for predicting the prognosis of ILD and its clinical course in PM/DM patients.

A 37-year-old man presented to the emergency room with fever, slurred speech and a 4-day history of progressively worsening headache. His medical history was unremarkable. He was not on any drug treatment. He described the headaches as dull, mild, constant, holocephalic and without focal features. On examination, his temperature was 39.2°C, blood pressure was 108/62 mm Hg, pulse was 106 beats per min, oxygen saturation was 92% (ambient air) and respiratory rate was 40 breaths per min. He was awake and oriented, with slow responses. Chest auscultation revealed bronchial sounds at the right …