巽 浩一郎

AIMS: The strong cytochrome P450 (CYP) 2C8 inhibitor gemfibrozil has been demonstrated to increase the area under the plasma concentration-time curve from 0 to infinity (AUC0-∞ ) of ACT-333679, an active metabolite of selexipag, by 11-fold. Similarly to gemfibrozil, the CYP2C8 inhibitor clopidogrel increased ACT-333679 concentration by 1.9-fold after a single loading dose (300 mg once daily) and 2.7-fold after repeated treatment with the maintenance dose (75 mg once daily) in Europeans. However, the effects of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 have not been fully elucidated in the Japanese population. METHODS: We investigated the effect of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 in 14 healthy Japanese volunteers. RESULTS: The concomitant administration of clopidogrel with selexipag did not influence the maximum concentration and AUC0-∞ of selexipag, whereas it significantly increased AUC0-∞ of ACT-333679 by approximately 1.90-fold (90% confidence interval 1.69-2.14) without changing the maximum concentration. When selexipag was administered 1 day after clopidogrel was discontinued, the increase in AUC0-∞ of ACT-333679 was 1.37-fold (90% confidence interval 0.93-2.02), suggesting that, although the inhibitory effect of clopidogrel on CYP2C8 was reduced, it persisted for at least 1 day after withdrawal. CONCLUSION: Our results demonstrated the impact of clopidogrel on the pharmacokinetics of selexipag and its active metabolite and suggested that selexipag should be carefully prescribed with clopidogrel with dose adjustment or reducing the dosing frequency in Japanese clinical settings.

It is generally considered that there is an increase in glycolysis in the hypertrophied right ventricle (RV) during pulmonary hypertension (PH), which leads to a decrease in glucose oxidation through the tricarboxylic acid (TCA) cycle. Although recent studies have demonstrated that fatty acid (FA) and glucose accumulated in the RV of patients with PH, the details of this remain to be elucidated. The purpose of the current study was to assess the metabolic remodeling in the RV of rats with PH using a metabolic analysis. Male rats were treated with the vascular endothelial growth factor receptor blocker SU5416 followed by 3 weeks of hypoxic conditions and 5 weeks of normoxic conditions (Su/Hx rats). Hemodynamic measurements were conducted, and the RV was harvested for the measurement of metabolites. A metabolomics analysis revealed a decreasing trend in the levels of alanine, argininosuccinic acid and downstream TCA cycle intermediates, including fumaric and malic acid and an increasing trend in branched‑chain amino acids (BCAAs) in Su/Hx rats compared with the controls; however, no trends in glycolysis were indicated. The FA metabolomics analysis also revealed a decreasing trend in the levels of long‑chain acylcarnitines, which transport FA from the cytosol to the mitochondria and are essential for beta‑oxidation. The current study demonstrated that the TCA cycle was less activated because of a decreasing trend in the expression of fumaric acid and malic acid, which might be attributable to the expression of adenylosuccinic acid and argininosuccinic acid. These results suggest that dysregulated BCAA metabolism and a decrease in FA oxidation might contribute to the reduction of the TCA cycle reactions.

BACKGROUND: There is limited evidence for pulmonary arterial hypertension (PAH)-targeted therapy in patients with pulmonary hypertension associated with respiratory disease (R-PH). Therefore, we conducted a multicenter prospective study of patients with R-PH to examine real-world characteristics of responders by evaluating demographics, treatment backgrounds, and prognosis.Methods and Results:Among the 281 patients with R-PH included in this study, there was a treatment-naïve cohort of 183 patients with normal pulmonary arterial wedge pressure and 1 of 4 major diseases (chronic obstructive pulmonary diseases, interstitial pneumonia [IP], IP with connective tissue disease, or combined pulmonary fibrosis with emphysema); 43% of patients had mild ventilatory impairment (MVI), whereas 52% had a severe form of PH. 68% received PAH-targeted therapies (mainly phosphodiesterase-5 inhibitors). Among patients with MVI, those treated initially (i.e., within 2 months of the first right heart catheterization) had better survival than patients not treated initially (3-year survival 70.6% vs. 34.2%; P=0.01); there was no significant difference in survival in the group with severe ventilatory impairment (49.6% vs. 32.1%; P=0.38). Responders to PAH-targeted therapy were more prevalent in the group with MVI. CONCLUSIONS: This first Japanese registry of R-PH showed that a high proportion of patients with MVI (PAH phenotype) had better survival if they received initial treatment with PAH-targeted therapies. Responders were predominant in the group with MVI.

BACKGROUND: Portopulmonary hypertension (PoPH) refers to the simultaneous presentation of pulmonary arterial and portal hypertension. However, few reports have included the characteristics and treatments for patients with PoPH of Asian population; thus, we investigated the clinical characteristics, treatment, and survival of these patients in a Japanese cohort. METHODS: Pulmonary arterial hypertension (PAH) has been included in the National Research Project on Intractable Disease in Japan; therefore, we extracted data of patients with PoPH from the forms of newly registered cases of the project from 2012 to 2013 (for 2 years), and updated cases of the project in 2013 (Study 1, n = 36 newly registered forms, n = 46 updated forms). Additionally, for Study 2, we performed a retrospective, observational cohort study at Chiba University Hospital (n = 11). We compared the characteristics between patients with PoPH and those with idiopathic/heritable PAH (I/H-PAH). RESULTS: Both studies showed higher cardiac outputs (COs) and cardiac indexes (CIs), lower pulmonary vascular resistance (PVR), and less treated with combination therapy in patients with PoPH than those with I/H-PAH. In Study 2, the overall and disease-specific survival between PoPH and I/H-PAH were similar. Conversely, many patients (45%) had to change their PAH-specific medicine because of adverse effects. CONCLUSION: As seen in western countries, Japanese patients with PoPH showed higher COs and CIs, better exercise tolerance, and lower PVRs than patients with I/H-PAH. Further studies are needed to improve PoPH treatments.

背景.気管支鏡検査の鎮静における塩酸ペチジン単独(P群)に対するミダゾラム併用(M+P群)の有効性と安全性の違いについては明らかではない.方法.2015年9月から2017年3月までに,当院で入院気管支鏡検査を行った症例のうち,同意が得られた症例(209例)に対して,気管支鏡再検査の忍容性について,質問票を用いて検討した結果を報告している.今回はpost hoc解析として同研究の対象となった209例をP群とM+P群の2群に分け,患者背景,診断率,合併症および質問票への回答の再解析を行った.結果.全209例中,P群は81例(39%),M+P群は128例(61%)であった.P群とM+P群で比較し,診断率(65% vs 73%,p=0.21),合併症の発生率(14% vs 12%,p=0.67)に有意差はなかった.質問票への回答としては,P群に比してM+P群で有意に苦痛度が低く(2.2±1.1 vs 2.9±1.2,p<0.001),想定より苦しくなく(2.0±1.0 vs 2.6±1.3,p<0.001),再検査の忍容性が高かった(2.5±1.3 vs 3.0±1.3,p=0.010).検査中の苦痛について,P群に比して,M+P群では苦痛がなかったと答えた例が多かった(35% vs 51%,p=0.02).苦痛の内容として,P群では咳嗽を挙げた例が最多であったが(23%),M+P群では検査前の咽頭麻酔を挙げる例が多かった(29%).結語.気管支鏡検査におけるミダゾラムとペチジンの併用による鎮静は,本邦でのミダゾラムとフェンタニルによる鎮静の前向き介入試験で示された忍容性と安全性と類似した結果を示し,有力な鎮静法の一つと考えられた.(著者抄録)

背景.気管支鏡検査の鎮静における塩酸ペチジン単独(P群)に対するミダゾラム併用(M+P群)の有効性と安全性の違いについては明らかではない.方法.2015年9月から2017年3月までに,当院で入院気管支鏡検査を行った症例のうち,同意が得られた症例(209例)に対して,気管支鏡再検査の忍容性について,質問票を用いて検討した結果を報告している.今回はpost hoc解析として同研究の対象となった209例をP群とM+P群の2群に分け,患者背景,診断率,合併症および質問票への回答の再解析を行った.結果.全209例中,P群は81例(39%),M+P群は128例(61%)であった.P群とM+P群で比較し,診断率(65% vs 73%,p=0.21),合併症の発生率(14% vs 12%,p=0.67)に有意差はなかった.質問票への回答としては,P群に比してM+P群で有意に苦痛度が低く(2.2±1.1 vs 2.9±1.2,p<0.001),想定より苦しくなく(2.0±1.0 vs 2.6±1.3,p<0.001),再検査の忍容性が高かった(2.5±1.3 vs 3.0±1.3,p=0.010).検査中の苦痛について,P群に比して,M+P群では苦痛がなかったと答えた例が多かった(35% vs 51%,p=0.02).苦痛の内容として,P群では咳嗽を挙げた例が最多であったが(23%),M+P群では検査前の咽頭麻酔を挙げる例が多かった(29%).結語.気管支鏡検査におけるミダゾラムとペチジンの併用による鎮静は,本邦でのミダゾラムとフェンタニルによる鎮静の前向き介入試験で示された忍容性と安全性と類似した結果を示し,有力な鎮静法の一つと考えられた.(著者抄録)

BACKGROUND: Cellular patterns in bronchoalveolar lavage fluid (BALF) are used to distinguish or rule out particular diseases in patients with acute respiratory failure (ARF). However, whether BALF cellular patterns can predict mortality or not is unknown. We test the hypothesis that BALF cellular patterns have predictive value for mortality in patients with ARF. METHODS: This was a retrospective single-center observational study conducted in a Japanese University Hospital. Consecutive patients (n = 78) with both pulmonary infiltrates and ARF who were examined by bronchoalveolar lavage (BAL) between April 2015 and May 2018 with at least 1 year of follow-up were analyzed. Primary analysis was receiver operating characteristic curve-area under the curve (ROC-AUC) analysis for 1-year mortality. RESULTS: Among the final sample size of 78 patients, survivors (n = 56) had significantly increased lymphocyte and eosinophil counts and decreased neutrophil counts in BALF compared with non-survivors (n = 22). Among the fractions, lymphocyte count was the most significantly different (30 [12-50] vs. 7.0 [2.9-13]%, P <0.0001). In the ROC curve analysis of the association of BALF lymphocytes with 1-year mortality, the AUC was 0.787 (P <0.0001, cut-off value [Youden index] 19.0%). Furthermore, ≥20% BALF lymphocytes were significantly associated with increased survival with adjustment for baseline imbalances (1-year adjusted hazard ratio, 0.0929; 95% confidence interval, 0.0147-0.323, P <0.0001; 90-day P =0.0012). Increased survival was significantly associated with ≥20% BALF lymphocytes in both interstitial lung disease (ILD) and non-ILD subgroups (P =0.0052 and P =0.0033, respectively). In secondary outcome analysis, patients with ≥20% BALF lymphocytes had significantly increased ventilator-free days, which represents less respiratory dysfunction than those with <20% BALF lymphocytes. CONCLUSIONS: In the patients with ARF, ≥20% lymphocytes in BALF was associated with significantly less ventilatory support, lower mortality at both 90-day and 1-year follow-ups.

BACKGROUND: Since there was no previous report, we analyzed the relationship between French Risk Stratification parameters in pulmonary arterial hypertension (PAH) and mean pulmonary arterial pressures (mPAP) using Japan PH Registry (JAPHR) national-wide cohort. METHODS: We enrolled 108 patients with PAH from JAPHR from previous reported cohort and analyzed the relations between French Risk Stratification scores and hemodynamic improvements. RESULTS: The ratio meeting 0 to 4 French Risk Stratification score was 21.3%, 31.5%, 32.4%, 13.0%, and 1.9% at baseline, and 6.5%, 23.2%, 33.3%, 23.2%, 13.9% at follow-up, respectively. The improvements in the number of criteria met were associated both with mPAP at follow-up (p = 0.03) and with the improvements in mPAP (p < 0.001). CONCLUSION: The improvements in French Risk Stratification may become a marker of improved hemodynamics including mPAP.

Heritable pulmonary arterial hypertension (HPAH) is a type of familial pulmonary arterial hypertension, while pulmonary arteriovenous malformations (PAVMs) are abnormal communications between pulmonary arteries and veins that occur frequently in patients with hereditary hemorrhagic telangiectasia (HHT). A 21-year-old woman on continuing medication for HPAH was hospitalized. She had been diagnosed with HPAH at age 4 years and had been receiving epoprostenol infusion from age of 9 years. Although lung perfusion scintigraphy showed a shunt fraction of 18.9% at age of 19 years, the cause of the shunt was unclear. At the time of the present hospitalization, enhanced computed tomography (CT) of the chest and four-dimensional reconstructed images revealed multiple abnormal communications between the peripheral pulmonary arteries and veins. Furthermore, right heart catheterization revealed an elevated mean pulmonary arterial pressure. Wedged angiography of the pulmonary artery of the right lower lobe revealed several PAVMs. Multiple PAVMs and suspected HHT with HPAH was diagnosed. The possibility of PAVMs should be considered even in patients with HPAH. Moreover, evaluation of the shunt fraction by lung perfusion scintigraphy and morphological examination of PAVM by contrast-enhanced CT may facilitate PAVM detection in patients with HPAH.

Background: Establishing the efficacy of novel photosensitizers (PSs) for phototherapy of lung cancer requires in vivo study prior to clinical evaluation. However, previously described animal models are not ideal for assessing transbronchial approaches with such PSs. Methods: An ultra-small parallel-type composite optical fiberscope (COF) with a 0.97 mm outer diameter tip. The integration of illumination and laser irradiation fibers inside the COF allows simultaneous white-light and fluorescence imaging, as well as real-time monitoring of tip position during laser phototherapy. An orthotopic lung cancer mouse model was created with three human lung cancer cell lines transbronchially inoculated into athymic nude mice. The COF was inserted transbronchially into a total of 15 mice for tumor observation. For in vivo fluorescence imaging, an organic nanoparticle, porphysome, was used as a PS. Laser excitation through the COF was performed at 50 mW using a 671 nm source. Results: The overall success rate for creating orthotopic lung tumors was 71%. Transbronchial white light images were successfully captured by COF. Access to the left main bronchus was successful in 87% of mice (13/15), the right main bronchus to the cranial lobe bronchus level in 100% (15/15), and to the right basal trifurcation of the middle lobe, caudal lobe and accessory lobe in 93% (14/15). For transbronchial tumor localization of orthotopic lung cancer tumors, PS-laden tumor with the strong signal was clearly contrasted from the normal bronchial wall. Conclusions: The ultra-small COF enabled reliable transbronchial access to orthotopic human lung cancer xenografts in vivo. This method could serve as a versatile preclinical research platform for PS evaluation in lung cancer, enabling transbronchial approaches in in vivo survival models inoculated with human lung cancer cells.

INTRODUCTION: Bronchoalveolar lavage (BAL) is useful for diagnosing diffuse lung disease and excluding other conditions. However, acute exacerbations (AEs) are recognized as important complications of BAL in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to identify risk factors for BAL-induced AEs in patients with IPF. MATERIAL AND METHODS: We retrospectively analyzed the data of 155 patients with suspected IPF who had undergone BAL between January 2013 and December 2018. BAL-related AE was defined as the development of AE within 30 days after the procedure. We compared clinical features and parameters between patients with AE (AE group) and without AE (non-AE group). We also reviewed the relevant reported literature. RESULTS: Among the 155 patients, 5 (3.2%) developed AE within 30 days after BAL. The average duration from BAL to AE onset was 7.8 days (2-16 days). Results from the univariate analysis revealed PaO2 < 75 mm Hg (p = 0.036), neutrophil content in BAL ≥ 7% (p = 0.0061), %DLCO < 50% (p = 0.019), Gender-Age-Physiology (GAP) stage III (p = 0.034), and BAL recovery rates < 30% (p < 0.001) as significant risk factors for post-BAL AE. All five patients who developed AE recovered and were discharged. CONCLUSIONS: Disease severity, high neutrophil levels in BAL, and poor BAL recovery rates may be risk factors for BAL-induced AEs.

Excessive release of neutrophil extracellular traps (NETs) has been implicated in several organ fibrosis, including pulmonary fibrosis. NETs constitute a phenomenon in which decorated nuclear chromatin with cytosolic proteins is released into the extracellular space. PAD4 (peptidylarginine deiminase 4) plays an important role in the formation of NETs. However, the role of NETs in the pathogenesis of pulmonary fibrosis remains undefined. Here, we identified NETs in the alveolar and interstitial lung space of mice undergoing bleomycin (BLM)-induced lung fibrosis, which was suppressed by a pan-PAD inhibitor, Cl-amidine. In vitro, BLM directly induced NETs in blood neutrophils, which was also inhibited by Cl-amidine. Furthermore, Padi4 gene knockout (PAD4-KO) in mice led to the alleviation of BLM-induced NETs and pulmonary fibrosis and to the expression of inflammatory and fibrotic genes. PAD4 deficiency prevented decreases in alveolar epithelial and pulmonary vascular endothelial cell numbers and increases in ACTA2-positive mesenchymal cells and S100A4-positive fibroblasts in the lung. Hematopoietic cell grafts from PAD4-KO mice, not wild-type mice, resolved BLM-induced lung fibrosis and fibrotic gene expression in wild-type and PAD4-KO mice, suggesting that expression of PAD4 in hematopoietic cells may be involved in the development of lung fibrosis. These data suggest that PAD4 deficiency could ameliorate BLM-induced formation of NETs and lung fibrosis, suggesting that this pathway could serve as a therapeutic target for pulmonary fibrosis treatment.

Pulmonary arteriovenous malformation (PAVM) is a potential cause of hemothorax. The risk of PAVM rupture is reported to be higher during pregnancy for several reasons, including increased body fluid and a change in hormonal conditions. A 34-year-old pregnant woman suddenly felt right chest pain and dyspnea in the 28th week of gestation. Chest X-ray and computed tomography showed massive right pleural effusion. Her vital signs gradually deteriorated with hemorrhagic shock, necessitating emergency surgery. During exploratory thoracoscopy, active bleeding from the middle lobe was noticed and gauze packing was required to maintain her blood pressure. Following conversion to major thoracotomy, wedge resection of the middle lobe was performed with a linear stapler, and finally, her general condition became stable. Her postoperative course was uneventful. A histological examination of the resected specimen confirmed the diagnosis of ruptured PAVM. Her baby was successfully delivered at the 38th week of gestation.

STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is caused by the paired-like homeobox 2B (PHOX2B) mutation and predominantly diagnosed during the neonatal period. Although late-onset CCHS and PHOX2B mutation carriers have been reported, the features of these disease states in adults remain uncertain. This study aimed to identify the characteristics of adult-onset CCHS and PHOX2B-mutation carriers in adult. METHODS: We mainly searched the PubMed/Medline and Cochrane Databases and classified our target patients into 2 groups: group A, symptomatically diagnosed with late-onset CCHS in adulthood; group B, adult PHOX2B-mutation carriers. Then, clinical characteristics, including the onset, treatment, long-term course, and pattern of the PHOX2B mutation in both groups were analyzed. Additionally, a new adult-case of late-onset CCHS was added to the analysis. RESULTS: Group A was comprised of 12 patients. The onset triggers of illness included a history of respiratory compromise following general anesthesia and respiratory tract infections. All patients in group A had 20/25 polyalanine repeat mutations and required some chronic ventilatory support at least during sleep, including portable positive pressure ventilator via tracheostomy or noninvasive positive pressure ventilation. In these patients with ventilatory support during sleep, sudden death or poor prognosis was not reported. Group B was comprised of 33 adults from 24 families with PHOX2B mutations. Nine patients in group B were confirmed with the diagnosis of CCHS. Although polyalanine repeat mutations 20/25 represented the most common gene mutation, diverse mutations, including mosaicism, were observed. Hypoventilation of several cases in group B were underdiagnosed by overnight polysomnography without monitoring for CO₂. CONCLUSION: Alveolar hypoventilation with unknown origin can be caused by the PHOX2B mutation even in adult cases. Both the identification of the PHOX2B mutation and the incorporation of capnography in polysomnography are important for adult cases with unexplained alveolar hypoventilation or asymptomatic mutation carriers.

This study investigated whether dilated bronchial arteries are associated with reperfusion pulmonary edema in patients with chronic thromboembolic pulmonary hypertension. Results showed that the extent of enlarged bronchial arteries was not associated with the development of reperfusion pulmonary edema, whereas the residual pulmonary hypertension had a significant association.

Introduction: An increased risk of sarcoidosis and sarcoid-like reactions in subjects with a history of malignancy has been suggested. We assessed the incidence and clinical characteristics of cancer patients with biopsies containing sarcoid-like granulomas on cancer metastasis and patient survival. Methods: This is a retrospective, multicentre, observational study involving endobronchial ultrasound transbronchial needle aspiration and a melanoma patient dataset at the University of Miami, USA, and a sarcoidosis patient database at Chiba University, Japan. Subjects with a confirmed diagnosis of cancer and who subsequently developed granulomas in different organs were enrolled. The study was registered at Clinicaltrials.gov (NCT03844698). Results: 133 patients met the study's criteria. The most common primary cancer sites were the skin (22.5%), breast (20.3%) and lymph node (12.8%). 24 (18%) patients developed sarcoid-like granulomas within 1 year of cancer diagnosis, 54 (40.6%) between 1 and 5 years and 49 (36.8%) after 5 years. Imaging showed possible sarcoid-like granulomas in lymph nodes in 51 cases (38.3%) and lung tissue and mediastinal lymph nodes in 73 cases (54.9%); some parenchymal reticular opacity and fibrosis was found in 5 (3.7%) and significant parenchymal fibrosis in 2 (1.5%) subjects. According to logistic regression analysis, the frequency of metastatic cancer was significantly lower in patients with sarcoid-like granulomas than in controls. Moreover, multivariate Cox proportional hazard analysis showed a significant survival advantage in those with sarcoid-like granuloma. Conclusion: Sarcoid-like granulomas are uncommon pathology findings in cancer patients. There is a significant association between the presence of granulomas and reduced metastasis and increased survival. Further study is warranted to understand the protective mechanism involved.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease that is caused by the dysregulation of alveolar epithelial type II cells (AEC II). The mechanisms involved in the progression of IPF remain incompletely understood, although the immune response accompanied by p38 mitogen-activated protein kinase (MAPK) activation may contribute to some of them. This study aimed to examine the association of p38 activity in the lungs with bleomycin (BLM)-induced pulmonary fibrosis and its transcriptomic profiling. Accordingly, we evaluated BLM-induced pulmonary fibrosis during an active fibrosis phase in three genotypes of mice carrying stepwise variations in intrinsic p38 activity in the AEC II and performed RNA sequencing of their lungs. Stepwise elevation of p38 signaling in the lungs of the three genotypes was correlated with increased severity of BLM-induced pulmonary fibrosis exhibiting reduced static compliance and higher collagen content. Transcriptome analysis of these lung samples also showed that the enhanced p38 signaling in the lungs was associated with increased transcription of the genes driving the p38 MAPK pathway and differentially expressed genes elicited by BLM, including those related to fibrosis as well as the immune system. Our findings underscore the significance of p38 MAPK in the progression of pulmonary fibrosis.

BACKGROUND: Although recent studies have identified anti-glycopeptidolipid (GPL)-core IgA antibodies as a serodiagnostic test for Mycobacterium avium complex lung disease (MAC-LD), this test shows insufficient sensitivity. This study aimed to determine the clinical utility of these antibodies in assessing disease progression and the clinical characteristics of MAC-LD patients with negative antibody results. METHODS: We retrospectively reviewed the medical records of consecutive newly diagnosed, untreated MAC-LD patients in two referral hospitals. We evaluated the association of anti-GPL-core IgA antibody results with disease progression requiring treatment and the factors associated with negative antibody results. RESULTS: In total, 229 patients (161 females; median age, 71 years; 185 with nodular/bronchiectatic disease phenotype; 69 with cavitary lesions) were enrolled; 146 patients (64%) were anti-GPL-core IgA antibody-positive. Radiological severity scores were associated with anti-GPL-core IgA antibody titers. During the median 364-day follow-up, 114 patients (49.8%) required treatment. Multivariate Cox proportional hazards analysis showed that positive anti-GPL-core IgA antibody results, a younger age, the absence of malignancy, and the presence of cavitary lesions were associated with disease progression requiring treatment. Multivariate logistic analysis revealed that significant factors related to the negative antibody results included underlying pulmonary disease, lower radiological scores, chronic sinusitis, and macrolide monotherapy. CONCLUSION: In addition to cavitary lesions, anti-GPL-core IgA antibody positivity was associated with disease progression requiring treatment. Physicians should carefully use anti-GPL-core IgA antibody results for the diagnosis of patients with underlying pulmonary disease, chronic sinusitis, macrolide monotherapy, and lower radiological severity.

BACKGROUND: The short-term efficacy of pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD) has been established. Although continuous follow-up and sustained exercise training is important to maintain the effects, the long-term efficacy of PR without frequent supervised training remains unclear. The aim of this meta-analysis was to investigate the long-term efficacy of PR with home-based or low frequent maintenance program on exercise capacity and health related quality of life (HRQOL) in patients with COPD. METHODS: We identified randomized controlled trials (RCTs) comparing long-term efficacy of PR with home-based or low frequent maintenance and no maintenance program from PubMed and the Cochrane Library. Primary outcomes were exercise capacity [6-minute walking distance (6MWD), incremental shuttle walking test (ISWT)] and HRQOL [St. George's Respiratory Questionnaire (SGRQ)]. Outcomes were combined using a random-effects model. This study is registered with PROSPERO, number CRD42019109718. RESULTS: Seven RCTs with a total of 492 patients with COPD met the inclusion criteria. PR with maintenance significantly improved 6MWD [mean difference (MD) 27.00; 95% CI: 1.04-52.96; P=0.01] and ISWT (MD 44.48; 95% CI: 30.70-58.25; P<0.01), however no statistical evidence of improvement in HRQOL (MD -1.32; 95% CI: -7.71 to 5.08, P=0.69) was observed. CONCLUSIONS: PR with maintenance programs appears to be more effective than without maintenance for preserving exercise capacity in the long-term in patients with COPD. No long-term efficacy on HRQOL were noted. To maintain the efficacy of PR on exercise capacity and HRQOL over a long duration, it might be necessary to reexamine the contents and frequency of maintenance programs.

目的:クリニカルクラークシップ(CC)における文献検索の現状と講義の効果を検証した。方法:対象は2019年5〜12月に呼吸器内科CCに参加した医学生67名。CC中に文献検索に関するアンケートと講義を実施した。結果:医学生はPubMedの使用頻度が多いが、利用する文献は日本語教科書、ガイドラインが多く、文献の吟味、英語読解に困難を感じていた。また、講義の前後で文献検索リテラシーの自己評価は有意に向上し、課題への引用文献数が前年度から増加した。結論:医学生は英語も含め文献検索は行うが文献の吟味や英語読解に困難を感じていた。また、講義でも文献検索リテラシーの向上が得られる可能性が示唆された。(著者抄録)

A 70-year-old male was referred to our hospital with lower limb muscle weakness and numbness of the left hand. The patient had previously been diagnosed seven years ago with lung cancer accompanied by central airway obstruction and had received chemoradiotherapy following placement of a metallic stent. Computed tomography (CT) scan revealed an osteolytic lesion which was adjacent to the fractured stent. T2-weighted magnetic resonance imaging (MRI) demonstrated high signal intensity in the disc space. The patient was diagnosed with spondylodiscitis and spinal epidural abscess related to the airway stent. Despite hemilaminectomy, laminectomy and long-term antibiotic therapy, the infection was uncontrolled. Moreover, osteolytic destruction and kyphotic deformity progressed. Removal of the airway stent was necessary; however, it was impossible because bronchial resection was required and the risk of mediastinal injury was considered to be high. The patient subsequently received palliative care. Long-term airway stenting can cause spondylodiscitis and spinal epidural abscess. Indications for the placement of metallic stents for malignant central airway obstruction should be carefully evaluated after considering the difficulty in removal and the long-term risk of severe complications. KEY POINTS: Significant findings of the study Long-term placement and fracture of the airway stent can cause spondylodiscitis and spinal epidural abscess. What this study adds The indication of placement of a metallic stent for malignant central airway obstruction should be considered with caution, especially if long-term survival can be expected.