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We report the synthesis and vapochromic behaviors of film materials consisting of hypervalent tin-containing π-conjugated polymers. We prepared copolymers with brominated tin-fused azobenzenes and modified fluorene having tetraethylene glycol as a side chain. The synthesized polymers showed good film-formability and high affinity with coordinating solvent molecules such as dimethyl sulfoxide (DMSO). In particular, we discovered distinct color changes from blue to purple when exposed to DMSO vapor. It was revealed that color changes should originate from reversible alteration of the coordination-number between five and six of hypervalent tin(IV) in the azobenzene compounds involved in the main-chain conjugation. Moreover, we also observed that binding constants between tin and coordinating solvents could be influenced by two substitutions on the tin atom and subsequently modulated responsivity of vapochromism in films by altering the type of substituent. Furthermore, the color-change behaviors can be estimated by quantum calculations with density functional theory. We demonstrate not only that hypervalent tin can work as a switching unit for modulating the electronic structures of π-conjugated polymers triggered by solvent coordination but also that vapochromic behaviors in films can be predicted by estimating the affinity between hypervalent tin and solvent molecules with theoretical calculations.

We demonstrate near-infrared (NIR) absorptive and emissive poly(p-phenylene vinylene) (PPV)-type π-conjugated polymers based on hypervalent tin-fused azobenzene (TAz) complexes. Taking advantage of the inherent narrow-energy gap of TAz complexes originating from the three-center four-electron (3c-4e) bond and nitrogen–tin (N–Sn) coordination, the synthesized polymers, TAz-PPVs, showed absorption, and emission in wavelength regions of >750 and 810 nm in diluted solution, respectively. From the experimental and theoretical investigations, the elevation of the highest occupied molecular orbital (HOMO) and the reduction of the lowest unoccupied molecular orbital (LUMO) were simultaneously shown to be caused by the extension of π-conjugation. The effective conjugation length was calculated to be n > 10 (n: degree of polymerization), and the value was comparable to conventional PPV systems. Through this research, we revealed that π-conjugated systems including hypervalent bonds were able to expand π-conjugation. According to the concept of “element blocks”, the development of heteroatom-containing narrow-energy-gap monomers should be a novel approach for the construction of new NIR-absorptive and emissive bland materials. Near-infrared (NIR) absorptive and emissive poly(p-phenylene vinylene) (PPV)-type π-conjugated polymers based on hypervalent tin-fused azobenzene (TAz) complexes were demonstrated. The synthesized polymers, TAz-PPVs, showed absorption and emission in wavelength regions of >750 and 810 nm in diluted solution, respectively, because of the inherent narrow-energy gap of TAz complexes originating from the three-center four-electron (3c-4e) bond and nitrogen–tin (N–Sn) coordination. Through this research, we revealed that π-conjugated systems including hypervalent bonds were able to expand π-conjugation.

ObjectivesThis study aimed to identify and investigate changes in the mortality of patients with chronic obstructive pulmonary disease (COPD) at the same institute from the 1990s to the 2000s. We hypothesised that the improvement in long-term mortality of COPD was achieved due to the development of pharmacological and non-pharmacological treatments.DesignThis study was a retrospective analysis of two observational prospective cohort studies. One study enrolled subjects from 1995 to 1997 (the 1990s), and the other enrolled subjects from 2005 to 2009 (the 2000s).SettingTwo studies from a single centre, which was the same university hospital in Japan.ParticipantsPatients with stable COPD.Primary and secondary outcome measuresWe analysed all-cause mortality data from the pooled database. Subanalyses were conducted by stratifying subjects into two groups according to airflow limitation severity as severe/very severe (per cent predicted value of forced expiratory volume in 1 s (%FEV1) 1≥50%).ResultsIn total, 280 male patients with COPD were enrolled. Patients in the 2000s (n=130) were significantly older (71.6 vs 68.7 years) and had milder disease (%FEV1; 57.6% vs 47.1%) than those in the 1990s (n=150). Almost all severe/very severe patients in the 2000s received long-acting bronchodilators (LABDs), and they had a significantly lower risk of mortality than those in the 1990s according to Cox proportional regression analyses (OR=0.34, 95% CI 0.13–0.78), with a 48% reduction in 5-year mortality (from 31.0% to 16.1%). Moreover, any LABD use had a significantly positive impact on prognosis, even after adjustments for age, FEV1, smoking status, dyspnoea, body size, oxygen therapy and study period.ConclusionsTrends indicating a better prognosis for patients with COPD in the 2000s were observed. This improvement may be associated with the usage of LABDs.

Background Most exacerbations of chronic obstructive pulmonary disease (COPD) are triggered by respiratory tract infections. Adaptive immunity via antibody production is important in preventing infections. Impaired antibody production is reported to be associated with an increased risk of exacerbations of COPD. In the present study, we elucidated whether reduced free light chains (FLCs), which are excessive amounts of light chains produced during antibody synthesis and can be used to estimate systemic antibody production, may be a promising biomarker to predict the risk of exacerbations of COPD. Methods We enrolled stable male patients with COPD and prospectively observed them for 2 years. At baseline, serum combined FLC (cFLC; sum of kappa and lambda values) and pulmonary function were evaluated. Exacerbation was defined as a worsening of symptoms requiring treatments with antibiotics, corticosteroids or both. Results 63 patients with stable COPD were enrolled (72.8±8.1 years, GOLD A/B/C/D=24/28/6/5), and 51 patients completed the 2-year follow-up. Serum cFLC was 31.1 mg·L−1 on average and ranged widely (1.4 to 89.9 mg·L−1). The patients with low cFLC (below the mean−sd, n=6) experienced a significantly shorter time to the first exacerbation of COPD (p, Impaired antibody production is associated with an increased risk for exacerbations of COPD. Low serum free light chain is a novel B-cell-associated biomarker for COPD exacerbations. https://bit.ly/35cgMTC

Background: Low antigravity muscle mass is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, the significance of longitudinal changes in antigravity muscle mass remains unclear in patients with COPD. Objectives: The aims of this study were to investigate the factors associated with the longitudinal loss of antigravity muscles and whether the accelerated loss of these muscles has a negative impact on prognosis. Methods: This study was part of a prospective observational study at Kyoto University. We enrolled stable male patients with COPD who underwent longitudinal quantitative CT analysis of the cross-sectional area of the erector spinae muscles (ESMCSA) at an interval of 3 years. The associations between the rate of change in ESMCSA (%ΔESM) and clinical parameters, such as anthropometry, symptoms, lung function, exacerbation frequency, and all-cause mortality, were investigated. Results: In total, 102 stable male COPD patients were successfully evaluated in this study (71.3 ± 8.3 years, GOLD stage I/II/III/IV = 20/47/28/7 patients). ESMCSA significantly decreased from 30.53 to 28.98 cm2 (p < 0.0001) in 3 years, and the mean %ΔESM was 5.21 ± 7.24%. The rate of survival during the observation period was 85.3% (87/102). Patients with an accelerated decline in ESMCSA (n = 31; more than double the mean rate of decline) had a significantly higher frequency of moderate-to-severe exacerbations during the interval (p = 0.015). They also had significantly worse survival (p = 0.035 by log-rank test). A multivariate Cox proportional hazard model showed that lower ESMCSA and greater %ΔESM decline were independently and significantly associated with mortality. Conclusions: Frequent exacerbations were related to the loss of antigravity muscles in COPD patients. The accelerated loss of antigravity muscles was associated with a poor prognosis.

Depression is a common and important comorbidity in patients with chronic obstructive pulmonary disease (COPD). Depressive status is associated with a high COPD assessment test (CAT) total score, but it is difficult to distinguish patients with depression from those with severe symptomatic COPD. We hypothesized that a non-respiratory symptom-dominant elevation in CAT score is associated with depression in patients with COPD.A total of 226 patients in the KYOTO cohort in Japan and 924 patients in the Korea COPD Subgroup Study (KOCOSS) cohort in the Republic of Korea were analyzed. Depression was diagnosed based on a PHQ-9 (patient health questionnaire-9) ≥5 in the KYOTO cohort and a BDI-II (Beck Depression Inventory-II) ≥17 in the KOCOSS cohort. Sums of respiratory symptoms (Q1-Q4; Q1234) and non-respiratory symptoms (Q5-Q8; Q5678) from CAT items were analyzed.Fifty-three (23.5%) patients in the KYOTO cohort and 111 (11.2%) patients in the KOCOSS cohort were identified as having depression. Fifty-five patients (24.3%) in the KYOTO cohort and 249 patients (26.9%) in the KOCOSS cohort showed non-respiratory symptom dominance (Q1234 ≤ Q5678), and they had a significantly higher prevalence of depression than did patients with respiratory symptom dominance (Q1234Q5678). Multivariable logistic regression analysis showed that both the CAT total score and Q1234 ≤ Q5678 were significantly associated with depression in both cohorts. Moreover, even in symptomatic patients (CAT total score ≥10), these significant associations were preserved.Non-respiratory symptom dominance in CAT is a suspicious feature for depression in patients with COPD.

Tracheobronchopathia osteochondroplastica is a rare benign condition in which multiple cartilaginous or bony submucosal nodules project into the trachea or bronchi. A 71-year-old man complained of cough for 3 months. Computed tomography scanning revealed a calcified tracheal tumor near the tracheal bifurcation. Pulmonary function testing indicated airflow limitation, and bronchoscopic examination confirmed a solitary rigid tumor. Bronchoscopic resection was performed under general anesthesia, and the tumor was detached by cauterizing its stem with high-frequency coagulation. The tumor was pathologically indicative of tracheobronchopathia osteochondroplastica. After surgery, the clinical signs of cough and dyspnea resolved and pulmonary function normalized.

BACKGROUND Some chronic obstructive pulmonary disease (COPD) patients develop hypoxemia with disease progression, with some even requiring long-term oxygen therapy (LTOT). Lung function, especially diffusing capacity, and the annual decline in PaO2, are reported to be predictive factors of chronic respiratory failure. However, the association between lung morphometry evaluated using computed tomography (CT) images and LTOT initiation is unknown. METHODS We retrospectively evaluated the relationship between clinical indices, including pulmonary function, body mass index (BMI), and CT parameters, at baseline and LTOT initiation in two prospective COPD cohorts. In the Nara Medical University cohort (n = 76), the low attenuation area (LAA) and its fractal dimension (fractal D) were adapted as the indices for parenchymal destruction in CT images. The association between these CT measurements and LTOT initiation was replicated in the Kyoto University cohort (n = 130). RESULTS In the Nara Medical University cohort, lower BMI (hazard ratio [HR]:0.70, p = 0.006), lower % diffusing capacity (%DLCO) (HR: 0.92, p = 0.006), lower %DLCO/VA (HR, 0.90, p = 0.008), higher RV/TLC (HR, 1.26, p = 0.012), higher LAA% (HR: 1.18, p = 0.001), and lower fractal D (HR: 3.27 × 10-8, p

We report the case of a 64-year-old man with advanced small-cell lung cancer who developed fulminant amoebic colitis during cytotoxic chemotherapy. During the first cycle of carboplatin/etoposide treatment, febrile neutropenia and grade 4 neutropenia developed. Because diarrhea, abdominal pain, and bloody stool were observed, abdominal computed tomography was performed, showing intussusception, and surgery was performed. Histopathology of the colon revealed gastrointestinal necrosis and perforation due to Entamoeba histolytica infection. Amoebiasis improved after treatment with metronidazole and paromomycin. The second cycle of carboplatin/etoposide with dose reduction was completed, resulting in a partial response to small-cell lung cancer. The results of this case suggest that paromomycin is an additional option for amoebiasis during cytotoxic chemotherapy, and persistent diarrhea during cytotoxic chemotherapy should alert clinicians to consider the development of amoebiasis. Funding declaration: None Conflict of Interests: None Consent: Written informed consent was obtained from the parents of the patient for the publication of this report and accompanying images

Background: Recent advances in quantitative chest CT have proposed novel indexes of airway disease, emphysema, and extra-pulmonary disorders in COPD. Loss of skeletal muscles is estimated as a reduction in the cross-sectional area of erector spinae muscles (ESMCSA) that is associated with physical inactivity and poor prognosis. This study tested a hypothesis that in clinical practice where physicians predict prognosis by combining pulmonary function, demographics, and CT findings, ESMCSA has greater predictive power than airway disease and emphysema assessments in COPD. Methods: Using data from a prospective observational study at Kyoto University Hospital, ESMCSA was measured on a CT image at the 12th thoracic vertebra. Total airway count (TAC), wall area percent of the segmental airways (WA%), airway tree to lung volume ratio (AWV%) were calculated to evaluate airway disease. Low attenuation volume percent (LAV%) and fractal dimension of low attenuation clusters (fractal D) were calculated to evaluate emphysema. Results: In total, 247 patients with COPD were enrolled from 2006 to 2012. The median follow-up period was 3295 days and 46 died. In multivariate cox proportional hazards models that adjusted for age, sex, body mass index, mMRC dyspnea scale, airflow limitation, and diffusion capacity, ESMCSA was associated with poor prognosis (hazard ratio [95% confidence interval] =1.3 [1.1-1.5] per 3.7mm2 reduction) more strongly than TAC, WA%, AWV%, LAV%, fractal D. Conclusion: The reduced ESMCSA can predict long-term mortality independent of pulmonary function and demographics. Exploring a preventive strategy against antigravity muscle loss might help improve COPD prognosis.

Rationale: Prolonged exercise intolerance is serious limiting factors for activity of daily living and quality of life of post lung transplantation (LTx). Although weakness of inspiratory muscle strength may contribute to exercise intolerance, it is unclear that inspiratory muscle strength is associated with a time course and/or recovery of exercise capacity after LTx. Aim: To elucidate what physical factors contribute much to recovery of exercise capacity during one year after LTx. Methods: We consecutively enrolled 24 patients who had LTx between June 2017 and September 2018 at Kyoto University Hospital. Exercise capacity (6MWD), quadriceps force (QF), inspiratory muscle strength (maximal inspiratory pressure; MIP), spirometory (VC, FEV1%) were evaluated at 3, 6, and 12 months after LTx. Factors which were associated with 6MWD recovery in 3 to 6 months and 6 to 12months were analyzed. Results: After LTx, BMI, QF, and 6MWD significantly improved continuously (BMI; 17.2/18.2/19.0 kg/m2, QF; 94/107/125 Nm and 6MWD; 468/498/512 m, at 3/6/12months, respectively). Mean MIP and VC showed significant improvement only between 3 and 12 months (MIP; 60 to 69 cmH2O and VC; 2.16 to 2.28L). Changes in MIP from 3 to 6 months after LTx demonstrated significant positive correlations with changes in 6MWD at same period by univariate (p Conclusion: It was suggested that approaches to inspiratory muscle strength might be helpful in recovery of exercise capacity at 3 to 6 months after LTx.

Multiple CT indices are associated with disease progression and mortality in patients with COPD, but which indices have the strongest association remain unestablished. This longitudinal 10-year observational study (n=247) showed that the emphysema severity on CT is more closely associated with the progression of airflow limitation and that a reduction in the cross-sectional area of erector spinae muscles (ESMCSA) on CT is more closely associated with mortality than the other CT indices, independent of patient demographics and pulmonary function. ESMCSA is a useful CT index that is more closely associated with long-term mortality than emphysema and airway disease in patients with COPD.

Previous studies have suggested a significant relationship between hyposalivation and inhalation therapy-induced oropharyngeal problems. However, salivary secretion tests are not widely performed in daily clinical practice. In fact, xerostomia, the complaint of dry mouth, may not indicate hyposalivation. Therefore, we determined the clinical factors associated with hyposalivation in patients with asthma.This study is a post-hoc analysis of our previous studies. Adult patients with asthma on maintenance inhalation therapy were enrolled. The participants completed questionnaires on oropharyngeal symptoms and underwent a salivary secretion test. Symptom severity was evaluated using a numerical rating scale (NRS), and salivary secretion was measured using the modified cotton roll method. Using logistic regression analysis, we identified the clinical factors associated with hyposalivation.In total, 531 patients completed the questionnaire (43.8 ± 16.9 years and male/female = 171/360), and 234 patients successfully performed a salivary secretion test, of which 126 (53.8%) were diagnosed with hyposalivation (0.25 g/min). The patients with hyposalivation were significantly older (p 0.0001) and had severe xerostomia and/or gastroesophageal reflux-like symptoms (GERLS) (p 0.0001). Many of these patients had also used inhaled long-acting beta agonists (p = 0.012) and high-dose inhaled corticosteroids (p = 0.024). Multivariate analysis revealed that advanced age (odds ratio [OR] 1.05, p 0.0001), severe xerostomia (OR 1.02, p = 0.0006) and severe GERLS (OR 1.02, p = 0.001) were independently and significantly associated with hyposalivation.Age, xerostomia, and GERLS were significantly related to hyposalivation in patients with asthma. To identify oropharyngeal problems in these patients, a careful assessment of the suspected symptoms of gastroesophageal reflux may be useful.

Epithelial dysfunction in the small airways may cause the development of emphysema in chronic obstructive pulmonary disease. C/EBPα (CCAAT/enhancer binding protein-α), a transcription factor, is required for lung maturation during development, and is also important for lung homeostasis after birth, including the maintenance of serine protease/antiprotease balance in the bronchiolar epithelium. This study aimed to show the roles of C/EBPα in the distal airway during chronic cigarette smoke exposure in mice and in the small airways in smokers. In a model of chronic smoke exposure using epithelial cell-specific C/EBPα-knockout mice, significant pathological phenotypes, such as higher protease activity, impaired ciliated cell regeneration, epithelial cell barrier dysfunction via reduced zonula occludens-1 (Zo-1), and decreased alveolar attachments, were found in C/EBPα-knockout mice compared with control mice. We found that Spink5 (serine protease inhibitor kazal-type 5) gene (encoding lymphoepithelial Kazal-type-related inhibitor [LEKTI], an anti-serine protease) expression in the small airways is a key regulator of protease activity in this model. Finally, we showed that daily antiprotease treatment counteracted the phenotypes of C/EBPα-knockout mice. In human studies, CEBPA (CCAAT/enhancer binding protein-α) gene expression in the lung was downregulated in patients with emphysema, and six smokers with centrilobular emphysema (CLE) showed a significant reduction in LEKTI in the small airways compared with 22 smokers without CLE. LEKTI downregulation in the small airways was associated with disease development during murine small airway injury and CLE in humans, suggesting that LEKTI might be a key factor linking small airway injury to the development of emphysema.

We herein report the case of a sixty-four-year-old woman with stage IV lung adenocarcinoma with thymoma. The adenocarcinoma showed 95% tumor proportion scores of PD-L1 (Programmed death-ligand 1) expression without driver mutations. She was treated with pembrolizumab as 1st-line chemotherapy. Creatine kinase elevation was observed on the 15th day, and fatal myocarditis developed on the 20th day despite steroid therapy. The autopsy showed lymphocyte-infiltrated cardiac muscle, and pembrolizumab-induced myocarditis was diagnosed. Our case indicates that lung cancer combined with thymoma should alert clinicians to monitor the early onset of myocarditis in patients on immune checkpoint inhibitor therapy.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31(+) CD45(−)cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant Staphylococcus aureus or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant S. aureus or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality. Since patients with severe COPD may experience exacerbations and eventually face mortality, advanced care planning (ACP) has been increasingly emphasized in the recent COPD guidelines. We conducted a multicenter, cross-sectional study to survey the current perspectives of Japanese COPD patients toward ACP. "High-risk" COPD patients and their attending physicians were consecutively recruited. The patients' family configurations, understanding of COPD pathophysiology, current end-of-life care communication with physicians and family members, and preferences for invasive life-sustaining treatments including mechanical ventilation (MV) and cardiopulmonary resuscitation (CPR) were evaluated using a custom-made, structured, self-administered questionnaire. Attending physicians were also interviewed, and we evaluated the patient-physician agreement. Among the 224 eligible "high-risk" patients, 162 participated. Half of the physicians (54.4%) thought they had communicated detailed information; however, only 19.4% of the COPD patients thought the physicians did so (κ score = 0.16). Less than 10% of patients wanted to receive invasive treatment (MV, 6.3% and CPR, 9.4%); interestingly, more than half marked their decision as "refer to the physician" (MV 42.5% and CPR 44.4%) or "refer to family" (MV, 13.8% and CPR, 14.4%). Patients with less knowledge of COPD were less likely to indicate that they had already made a decision. Although ACP is necessary to cope with severe COPD, Japanese "high-risk" COPD patients were unable to make a decision on their preferences for invasive treatments. Lack of disease knowledge and communication gaps between patients and physicians should be addressed as part of these patients' care.

Loss of skeletal muscle mass and physical inactivity are important manifestations of chronic obstructive pulmonary disease (COPD), and both are closely related to poor prognoses in patients with COPD. Antigravity muscles are involved in maintaining normal posture and are prone to atrophy with inactivity. The erector spinae muscles (ESM) are one of the antigravity muscle groups, and they can be assessed by chest computed tomography (CT).We hypothesized that the cross-sectional area of ESM (ESMCSA) visualized on chest CT images may serve as a predictor of mortality in patients with COPD.This study was part of the prospective observational study undertaken at Kyoto University Hospital. ESMCSA was measured on a single-slice axial CT image at the level of the 12th thoracic vertebra in patients with COPD. The cross-sectional area of the pectoralis muscles (PMCSA) was also measured. We evaluated the relationship between ESMCSA and clinical parameters, including mortality, in patients with COPD. Age- and height-matched smoking control subjects were also evaluated.In total, 130 male patients and 20 smoking control males were enrolled in this study. ESMCSA was significantly lower in patients with COPD than in the smoking control subjects and was significantly correlated with disease severity. There was a significant but only moderate correlation between ESMCSA and PMCSA. ESMCSA was significantly correlated with previously reported prognostic factors, such as body mass index, dyspnea (modified Medical Research Council dyspnea scale score), FEV1 percent predicted value, inspiratory capacity to total lung capacity ratio, and emphysema severity (percentage of the lung field occupied by low attenuation area). Compared with PMCSA, ESMCSA was more strongly associated with mortality in patients with COPD. Stepwise multivariate Cox proportional hazards analysis revealed that, among these known prognostic factors, ESMCSA was the strongest risk factor for mortality (hazard ratio, 0.85; 95% confidence interval, 0.79-0.92; P 0.001) and mMRC dyspnea scale score was an additional factor (hazard ratio, 2.35; 95% confidence interval, 1.51-3.65; P 0.001).ESMCSA assessed by chest CT may be a valuable clinical parameter, as ESACSA correlates significantly with physiological parameters, symptoms, and disease prognosis.

BACKGROUND AND OBJECTIVE Chronic respiratory failure (CRF) with hypoxaemia is an important pathophysiology in patients with chronic obstructive pulmonary disease (COPD), and existing mild hypoxaemia may be a sign of future CRF development. However, little is known about the trajectory of partial arterial pressure of oxygen (PaO2 ) decline in patients with COPD. We assessed decline in PaO2 and the impact of short-term reductions in PaO2 to predict future decline in PaO2 . METHODS A total of 172 outpatients with COPD from a prospective cohort study were enrolled. Pulmonary function tests and arterial blood gas (ABG) analyses were conducted at baseline and 1 year after enrolment and changes in PaO2 (ΔPaO2 ) and other parameters were calculated. Survival and incidence of CRF (as assessed by prescription of long-term home oxygen therapy) were monitored for 6 years. RESULTS A total of 164 patients completed the observation period and 101 patients had mild hypoxaemia (PaO2

Background and objective Chronic obstructive pulmonary disease (COPD) is characterized by a mixture of emphysema and airway disease. The forced oscillation technique (FOT) has been applied to COPD patients to clarify changes in respiratory mechanics; dynamic changes in respiratory resistance (Rrs) during breathing (within-breath changes in Rrs, ΔRrs) are characteristic of COPD. However, the pathophysiological significance of these changes is unknown. The aim of this study was to assess how emphysema and airway disease influence ΔRrs in COPD patients. Methods In this cross-sectional study, stable COPD patients were recruited and underwent respiratory impedance measurements with a commercially available FOT device. Rrs was recorded during tidal breathing and then analyzed as whole-breath Rrs (Rrs at 5 Hz, R5; Rrs at 20 Hz, R20; and their difference, R5−R20) or as ΔRrs, the difference between the expiratory and inspiratory Rrs (ΔR5, ΔR20 and ΔR5–R20). The percentage of the low attenuation area (LAA%) and airway wall area (WA%) was quantified by computed tomography analysis, and their contributions to ΔRrs were examined. Results Seventy-five COPD patients were recruited. LAA% was negatively correlated with ΔR5 and ΔR5−R20 (P = 0.0002 and P = 0.0033, respectively); meanwhile, WA% in B10 was positively correlated with ΔR5 and ΔR5−R20 (P = 0.0057 and P

Background Cough and sputum production (symptoms of bronchitis) are common in chronic obstructive pulmonary disease (COPD). Extrapulmonary comorbidities, such as gastroesophageal reflux disease (GERD) and post-nasal drip, also cause bronchitis symptoms. The impact of extrapulmonary comorbidities on the severity of bronchitis symptoms in COPD is unknown. The aim of this study was to quantify bronchitis symptoms and assess the impact of GERD and nasal symptoms on the severity of bronchitis symptoms in COPD. Methods In this cross-sectional study, stable COPD patients were recruited and completed the COPD assessment test (CAT) and Cough and Sputum Assessment Questionnaire (CASA-Q) to quantify bronchitis symptoms. To evaluate extrapulmonary comorbidities, the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and nasal symptom questionnaire were completed. The impact of these comorbidities on the severity of bronchitis symptoms was analyzed. Results Ninety-nine COPD patients were recruited. The presence of GERD symptoms (24.2% in the study population) was associated with more sputum symptoms. The presence of nasal discharge (43.4%) was associated with more cough and sputum symptoms, whereas post-nasal drip (13.1%) was associated with more sputum symptoms. On multivariate analyses, nasal discharge was associated with more cough symptoms. GERD and post-nasal drip were associated with more sputum symptoms. Conclusion This study showed that the presence of GERD and/or nasal symptoms is associated with an increase in bronchitis symptoms. Careful assessment of extrapulmonary comorbidities is necessary in the evaluation of bronchitis symptoms in COPD patients.

[Introduction] Impaired coordination between breathing and swallowing (breathing–swallowing discoordination) may be a significant risk factor for the exacerbation of chronic obstructive pulmonary disease (COPD). We examined breathing–swallowing discoordination in patients with COPD using a noninvasive and quantitative technique and determined its association with COPD exacerbation. [Methods] We recruited 65 stable outpatients with COPD who were enrolled in our prospective observational cohort study and did not manifest an apparent swallowing disorder. COPD exacerbation was monitored for 1 year before and 1 year after recruitment. Swallowing during inspiration (the I-SW pattern) and swallowing immediately followed by inspiration (the SW-I pattern) were identified. [Results] The mean frequency of the I-SW and/or SW-I patterns (I-SW/SW-I rate) was 21.5%±25.5%. During the 2-year observation period, 48 exacerbation incidents (25 patients) were identified. The I-SW/SW-I rate was significantly associated with the frequency of exacerbation. During the year following recruitment, patients with a higher I-SW/SW-I frequency using thicker test foods exhibited a significantly higher probability of future exacerbations (p=0.002, log-rank test). [Conclusions] Breathing–swallowing discoordination is strongly associated with frequent exacerbations of COPD. Strategies that identify and improve breathing– swallowing coordination may be a new therapeutic treatment for patients with COPD.

The airway epithelium acts as a frontline barrier against various environmental insults and its repair process after airway injury is critical for the lung homeostasis restoration. Recently, the role of intracellular reactive oxygen species (ROS) as transcription-independent damage signaling has been highlighted in the wound repair process. Both conditions of continuous hypoxia and intermittent hypoxia (IH) induce ROS. Although IH is important in clinical settings, the roles of IH-induced ROS in the airway repair process have not been investigated. In this study, we firstly showed that IH induced mitochondrial hydrogen peroxide (H2O2) production and significantly decreased bronchial epithelial cell migration, prevented by catalase treatment in a wound scratch assay. RhoA activity was higher during repair process in the IH condition compared to in the normoxic condition, resulting in the cellular morphological changes shown by immunofluorescence staining: round cells, reduced central stress fiber numbers, pronounced cortical actin filament distributions, and punctate focal adhesions. These phenotypes were replicated by exogenous H2O2 treatment under the normoxic condition. Our findings confirmed the transcription-independent role of IH-induced intracellular ROS in the bronchial epithelial cell repair process and might have significant implications for impaired bronchial epithelial cell regeneration.

Background The heterogeneous distribution of emphysema is a key feature of chronic obstructive pulmonary disease (COPD) patients that typically is evaluated using high-resolution chest computed tomography (HRCT). Oxygen-enhanced pulmonary magnetic resonance imaging (OEMRI) is a new method to obtain information regarding regional ventilation, diffusion, and perfusion in the lung without radiation exposure. We aimed to compare OEMRI with HRCT for the assessment of heterogeneity in COPD patients. Methods Forty patients with stable COPD underwent quantitative HRCT, OEMRI, and pulmonary function tests, including arterial blood gas analysis. OEMRI was also performed on nine healthy control subjects. We measured the severity of emphysema (percent low attenuation volume; LAV%) in whole lungs and the standard deviations (SDs) of the LAV% values of 10 isovolumetric partitions (SD-LAV) as an index of cranial-caudal heterogeneity. Similarly, relative enhancement ratios of oxygen (RERs) in whole lungs from OEMRI and SD-RER were analyzed. Results COPD patients showed a lower mean RER than control subjects (12.6% vs 22.0%, p