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Purpose: The present study evaluated the sex-specific susceptibility to the development of emphysema in patients with smoking histories who underwent lung cancer surgeries. Methods: Lung cancer patients with smoking histories who underwent lung resection at the University of Tsukuba Hospital, Japan, were enrolled. Radiologic emphysematous changes were analyzed using three-dimensional computed tomography (3D-CT). The volume proportion of emphysematous lung per unit of smoking and the relationship between emphysematous change and clinicopathologic factors were evaluated. Results: Radiologic emphysematous changes analyzed using 3D-CT per pack-year smoked, defined as the Smoking-Emphysema Index (SEI), were greater in females than males. The difference was more profound in adenocarcinoma patients than in non-adenocarcinoma patients (0.70 ± 2.30 vs. 0.21 ± 0.28, P = 0.037). Conclusion: Female lung cancer patients are more susceptible to smoking-induced emphysema than males. The SEI may be an effective indicator for evaluating smoking-induced emphysema. [ABSTRACT FROM AUTHOR]

Background and Objective: Mucus plugs and underlying airway tree structure can affect airflow limitation and prognosis in patients with chronic obstructive pulmonary disease (COPD), but their relative roles are unclear. This study used two COPD cohorts to examine whether mucus plugs on computed tomography (CT) were associated with airflow limitation and clinical outcomes independent of other airway structural changes and emphysema., Methods: Based on visual CT assessment, patients with mucus plugs in 0, 1-2 and ≥3 lung segments were assigned to no-, low- and high-mucus groups. Loss of health-related independence and mortality were prospectively recorded for 3 and 10 years in the Kyoto-Himeji and Hokkaido cohorts, respectively. The percentages of the wall area of the central airways (WA%), total airway count (TAC) and emphysema were quantified on CT., Results: Of 199 and 96 patients in the Kyoto-Himeji and Hokkaido cohorts, 34% and 30%, respectively, had high mucus scores. In both cohorts, TAC was lower in the high-mucus group than in the no-mucus group, whereas their emphysema severity did not differ. High mucus score and low TAC were independently associated with airflow limitation after adjustment for WA% and emphysema. In multivariable models adjusted for WA% and emphysema, TAC, rather than mucus score, was associated with a greater rate of loss of independence, whereas high mucus score, rather than TAC, was associated with increased mortality., Conclusion: Mucus plugs and lower airway branch count on CT had distinct roles in airflow limitation, health-related independence and mortality in patients with COPD., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Pulmonary emphysema is predominantly caused by chronic exposure to cigarette smoke (CS). Novel tobacco substitutes, such as heated tobacco products (HTPs), have emerged as healthier alternatives to cigarettes. IQOS, the most popular HTP in Japan, is advertised as harmless compared with conventional cigarettes. Although some studies have reported its toxicity, few in vivo studies have been conducted. Here, 12-wk-old C57BL6/J male mice were divided into three groups and exposed to air (as control), IQOS aerosol, or CS for 6 mo. After exposure, the weight gain was significantly suppressed in the IQOS and CS groups compared with the control ( –4.93 g; IQOS vs. air and –5.504 g; CS vs. air). The serum cotinine level was significantly higher in the IQOS group than in the control group. The neutrophils and lymphocyte count increased in the bronchoalveolar lavage fluid of the IQOS and CS groups compared with those in the control group. Chronic IQOS exposure induced pulmonary emphysema similar to that observed in the CS group. Furthermore, expression levels of the genes involved in the apoptosis-related pathways were significantly upregulated in the lungs of the IQOS-exposed mice. Cytochrome c, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase-1 were overexpressed in the IQOS group compared with the control. Single-stranded DNA and TdT-mediated dUTP nick-end labeling-positive alveolar septal cell count significantly increased in the IQOS group compared with the control. In conclusion, chronic exposure to IQOS aerosol induces pulmonary emphysema predominantly via apoptosis-related pathways. This suggests that HTPs are not completely safe tobacco products. [ABSTRACT FROM AUTHOR]

Background: The vertical P-wave axis on electrocardiography (ECG) is a useful criterion for screening patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the clinical characteristics of patients with COPD with a vertical P-wave axis as they have not yet been elucidated. Methods: Keio University and its affiliated hospitals conducted an observational COPD cohort study over 3 years. We analyzed 201 patients using ECG and chest computed tomography. Results: The severity of airflow limitation was higher in patients with a P-wave axis >75° than in those with a P-wave axis ≤75°. Patients with a P-wave axis >75° exhibited significantly higher total COPD assessment test scores and increased St. George's Respiratory Questionnaire total, activity, and impact scores than those with a P-wave axis ≤75°. The incidence of exacerbations over 1 and 3 years was significantly higher in patients with a P-wave axis >75° than in those with a P-wave axis ≤75°. The optimal cutoff for the P-wave axis for a percentage of the predicted forced expiratory volume in 1 s <50% and future exacerbations over 3 years was 70° (the areas under the curve [AUC]: 0.788; sensitivity: 65.3%; specificity: 78.3%) and 79° (AUC: 0.642; sensitivity: 36.7%; specificity: 92.6%). The ratio of the low attenuation area was also significantly higher in patients with a P-wave axis >75° than in those with a P-wave axis ≤75°. However, the ratio of the airway wall area did not differ between the 2 groups. Conclusions: Patients with COPD with a vertical P-wave axis exhibited severe airflow limitation and emphysema, a worse health status, and more frequent exacerbation than patients without a vertical P-wave. Detection of the vertical P-wave axis by ECG is beneficial for the management of patients with COPD. [ABSTRACT FROM AUTHOR]

Objective Bronchoscopic lung volume reduction (BLVR) using a one-way endobronchial valve (EBV) can provide clinically meaningful benefits to chronic obstructive pulmonary disease (COPD) patients. Although the Japanese Pharmaceuticals and Medical Devices Agency approved EBVs in November 2022, information regarding the number of Japanese patients with severe COPD eligible for BLVR treatment is still lacking. We therefore screened computed tomography (CT) images of patients with severe COPD using a quantitative CT (QCT) analysis to estimate the proportion of candidates eligible for BLVR treatment with an EBV. Methods CT scans of COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 3 and 4 were retrospectively analyzed using QCT to evaluate fissure integrity and tissue destruction. The difference in volume-weighted percentage was measured using the density scores of the target lobe and ipsilateral non-target lobe at -910 Hounsfield units. The target lobe was defined as the most affected lobe, with an emphysema destruction score of >50% for each patient. Results High-resolution CT scans of 32 patients (GOLD 3=19, GOLD 4=13) were analyzed. The target lobe could not be identified in 1 patient, whereas the target lobes for 8 patients were not surrounded by fissures with ≥80% completeness. Conversely, in 13 patients, the target lobes were surrounded by fissures with >95% completeness. The remaining 10 patients had fissure completeness between 80% and 95% at the target lobes and were considered candidates for collateral ventilation assessment. Conclusion A QCT analysis showed that 23 of 32 patients with severe COPD could be considered for a thorough examination of BLVR treatment with EBV.

Background: Although cigarette smoking may have a negative impact on the clinical outcome of pulmonary tuberculosis (PTB), few studies have investigated the impact of smoking-associated lung diseases. Emphysema is a major pathological finding of smoking-related lung damage. We aimed to clarify the effect of emphysema on sputum culture conversion rate for Mycobacterium tuberculosis (MTB).Methods: We retrospectively studied 79 male patients with PTB confirmed by acid-fast bacillus smear and culture at Jikei University Daisan Hospital between January 2015 and December 2018. We investigated the sputum culture conversion rates for MTB after starting standard anti-TB treatment in patients with or without emphysema. Emphysema was defined as Goddard score ≥ 1 based on low attenuation area < - 950 Hounsfield Unit (HU) using computed tomography (CT). We also evaluated the effect on PTB-related CT findings prior to anti-TB treatment.Results: Mycobacterial median time to culture conversion (TCC) in 38 PTB patients with emphysema was 52.0 days [interquartile range (IQR) 29.0-66.0 days], which was significantly delayed compared with that in 41 patients without emphysema (28.0 days, IQR 14.0-42.0 days) (p < 0.001, log-rank test). Multivariate Cox proportional hazards analysis showed that the following were associated with delayed TCC: emphysema [hazard ratio (HR): 2.43; 95% confidence interval (CI): 1.18-4.97; p = 0.015), cavities (HR: 2.15; 95% CI: 1.83-3.89; p = 0.012) and baseline time to TB detection within 2 weeks (HR: 2.95; 95% CI: 1.64-5.31; p < 0.0001). Cavities and consolidation were more often identified by CT in PTB patients with than without emphysema (71.05% vs 43.90%; p = 0.015, and 84.21% vs 60.98%; p = 0.021, respectively).Conclusions: This study suggests that emphysema poses an increased risk of delayed TCC in PTB. Emphysema detection by CT might be a useful method for prediction of the duration of PTB treatment required for sputum negative conversion. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the clinical characteristics and prognosis of acute exacerbation (AE) in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary emphysema., Design: A multicentre retrospective cohort study SETTING: Two university hospitals in Japan PARTICIPANTS: Patients admitted to hospitals due to AE of IPF diagnosed based on a multidisciplinary discussion., Interventions: None PRIMARY AND SECONDARY OUTCOME MEASURES: 90-day mortality rate METHODS: We retrospectively analysed consecutive patients with AE of IPF, with or without pulmonary emphysema, admitted to two university hospitals between 2007 and 2018., Results: Among 62 patients (median age, 75 years; 48 men) admitted for AE of IPF, 29 patients (46%) presented with concomitant pulmonary emphysema. There was no significant difference in the arterial partial oxygen pressure/fraction of inhaled oxygen (P/F) ratio or other laboratory and radiographic data between patients with and without emphysema. The 90-day mortality rate was significantly lower in patients with emphysema than in those with IPF alone (23% vs 52%, p=0.03). The median survival time was significantly longer in patients with emphysema than in those with IPF alone (405 vs 242 days, p=0.02)., Conclusion: Patients with IPF and emphysema had better short-term survival after AE than those with non-emphysematous IPF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Most patients with combined pulmonary fibrosis and emphysema ( CPFE) are males, and heavy smokers. CPFE is more prevalent than fibrosis in patients with lung cancer, and patients with CPFE usually have a poor prognosis. This study reviewed the differences in the prevalence of lung cancer among patients with normal, fibrosis, emphysema and CPFE via chest computed tomography ( CT), and the relationship between histopathology and the localizations of lung cancer. Methods Patients that were diagnosed with lung cancer confirmed by pathological examinations between 2003 and 2011 were retrospectively reviewed to obtain clinical, pathological, and radiological data. These patients were categorized into four groups based on chest CT findings: normal, fibrosis, emphysema and CPFE. Results Two hundred and seventy-four patients with lung cancer were classified into 146 normal, 14 fibrosis, 78 emphysema, and 36 CPFE groups. Combined centriacinar and paraseptal emphysema was common in the CPFE group. The prevalence of squamous cell carcinoma in the CPFE group was significantly higher in comparison to the normal group. The rate of peripheral localization of lung cancer in the CPFE group was significantly higher in comparison to the normal, fibrosis, and emphysema groups. The prevalence of squamous cell carcinoma of peripheral areas in the CPFE group was significantly higher in the normal and emphysema groups. Conclusions CPFE patients demonstrated histopathological and radiological differences concerning the histological types and localization of lung cancers. [ABSTRACT FROM AUTHOR]

Aim Age-associated changes of the lung might increase pathogenetic susceptibility to chronic obstructive pulmonary disease ( COPD). Decrement in serum transforming growth factor ( TGF)-β1 concentration is reported in elderly people. As impaired TGF-β1 signaling could cause emphysema-like changes, we hypothesized that decreased TGF-β1 with aging is correlated with emphysema. Methods Symptomatic patients with or without COPD and healthy normal subjects without COPD were recruited ( COPD, n = 182; smoking controls, n = 73; normal, n = 26). We investigated the correlation between TGF-β1 and extent of emphysema and airway wall thickness, which were defined as the percentage of low-attenuation area ( LAA%) and large airway wall area ( WA%) on pulmonary high-resolution computed tomography, respectively. The correlation of pulmonary function test parameters and TGF-β1 was evaluated. TGF-β1 was determined by enzyme-linked immunosorbent assay. Results TGF-β1 significantly decreased with age ( P = 0.0009). When the correlation between age and TGF-β1 was analyzed in each group, a significant inverse correlation was found in COPD patients and smoking controls ( P = 0.0095 and 0.0132, respectively), whereas no correlation was observed in healthy older adults. Among COPD patients with severe emphysema, LAA% was inversely correlated with TGF-β1 ( n = 89, P = 0.0104), whereas WA% and pulmonary function test parameters were not. Conclusions Although no correlation was found between TGF-β1 and the severity of COPD, TGF-β1 significantly decreased as emphysema became more severe. Age-related decrease of TGF-β1 in COPD might be associated with emphysematous alterations of the lungs in elderly subjects. Geriatr Gerontol Int 2013; 13: 1069-1075. [ABSTRACT FROM AUTHOR]

Background and objective: Symptom-based questionnaires may be helpful in diagnosing patients with COPD. The aim of this study was to determine whether two COPD questionnaires designed in Western countries were applicable to Japanese and other Asian patients. Methods: The participants were Japanese people aged 40 years and over. Each subject answered questions on demographics and symptoms and underwent spirometry before and after administration of a bronchodilator. Questionnaire A was designed to identify previously undiagnosed COPD and questionnaire B was designed to differentiate between COPD and asthma. Results: The numbers of COPD patients who answered questionnaires A and B were 33 of 169 (19.5%) and 112 of 168 (66.7%), respectively. Comparison of the COPD group with the non-COPD group revealed a significant difference in total score in both questionnaire A and questionnaire B (both P < 0.001). The area under the receiver operating characteristic curve (AUC-ROC) for questionnaire A was 0.791. With a cut-off value of 16.5 points, the sensitivity and specificity were 0.939 and 0.404, and with a 19.5-point cut-off, sensitivity and specificity were 0.848 and 0.647, respectively. The AUC-ROC for questionnaire B was 0.765. With cut-off values of 18.5 and 24.5 points, the respective sensitivities and specificities were 0.946 and 0.393, and 0.741 and 0.607. Conclusions: A simple self-administered questionnaire can help to diagnose COPD in Japanese subjects. When these questionnaires are used in Japan, cut-off values should be set somewhat higher than in Western countries. [ABSTRACT FROM AUTHOR]

Introduction: A better understanding is needed of the different phenotypes that exist for patients with chronic obstructive pulmonary disease (COPD), their relationship with the pathogenesis of COPD and how they may affect disease progression. Biomarkers, including those associated with emphysema, may assist in characterising patients and in predicting and monitoring the course of disease. The FOOTPRINTS study (study 352.2069) aims to identify biomarkers associated with emphysema, over a 3-year period., Methods and Analysis: The FOOTPRINTS study is a prospective, longitudinal, multinational (12 countries), multicentre (51 sites) biomarker study, which has enrolled a total of 463 ex-smokers, including subjects without airflow limitation (as defined by the 2015 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report), patients with COPD across the GOLD stages 1-3 and patients with COPD and alpha1-antitrypsin deficiency. The study has an observational period lasting 156 weeks that includes seven site visits and additional phone interviews. Biomarkers in blood and sputum, imaging data (CT and magnetic resonance), clinical parameters, medical events of special interest and safety are being assessed at regular visits. Disease progression based on biomarker values and COPD phenotypes are being assessed using multivariate statistical prediction models., Ethics and Dissemination: The study protocol was approved by the authorities and ethics committees/institutional review boards of the respective institutions where applicable, which included study sites in Belgium, Canada, Denmark, Finland, Germany, Japan, Korea, Poland, Spain, Sweden, UK and USA; written informed consent has been obtained from all study participants. Ethics committee approval was obtained for all participating sites prior to enrolment of the study participants. The study results will be reported in peer-reviewed publications., Trial Registration Number: NCT02719184., Competing Interests: Competing interests: JC is a co-prinicipal investigator for the COPDGene study and has received grants from National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI). AG, MB, BL, CI, FR and CD are employees of Boehringer Ingelheim. DAL has received grants from NHLBI, and personal fees from Boehringer Ingelheim, Parexel, Siemens and Veracyte. In addition, DAL has a patent for ‘systems and methods for classifying severity of COPD’ pending. HW has received grants and personal fees from Boehringer Ingelheim, and personal fees from AstraZeneca, Chiesi, GSK, Menarini and Novartis. JV-C has received grants and personal fees from Boehringer Ingelheim and Novartis, and grants from GSK and Siemens Healthineers. AMT has received personal fees, payment for educational talks and expenses payments for work on the FOOTPRINTS steering committee from Boehringer Ingelheim, grants and personal fees from AstraZeneca, CSL Behring and Grifols Biotheraputics, and grants, personal fees and non-finanacial support from Chiesi. RMM has received personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Merck Sharp & Dohme, Mundipharma, Novartis and Roche. WJ has received grants from AstraZeneca and Chiesi. AL-S reports receipt of a study fee for involvement in conducting the FOOTPRINTS study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Forced expiratory volume in 1 s (FEV 1 ) is a standard physiological index of chronic obstructive pulmonary disease (COPD), but reflects emphysema and vascular abnormalities less sensitively than diffusion capacity for carbon monoxide (D LCO ). This study tested whether a disproportionally impaired D LCO relative to FEV 1 (FEV 1 z -score>-3 and D LCO was available. The cross-sectional and longitudinal analyses of the Kyoto University Cohort (single-center study in Japan) included 195 males with COPD who were prospectively followed for 10 years. A disproportionally impaired D z -score≤-3) is a common functional COPD phenotype associated with distinct clinical and structural features and the prognosis of two cohorts. The cross-sectional analyses of the Korea COPD Subgroup Study (KOCOSS) cohort (multicenter study in Korea) included 743 males with COPD whose D LCO was available. The cross-sectional and longitudinal analyses of the Kyoto University Cohort (single-center study in Japan) included 195 males with COPD who were prospectively followed for 10 years. A disproportionally impaired D LCO was associated with worse symptoms, shorter 6-minute walking distance, paraseptal and centrilobular emphysema on computed tomography, and reduced arterial oxygen and carbon dioxide pressures compared to the reference (FEV 1 was observed in 29% and 31% of patients in the KOCOSS and Kyoto University cohorts, respectively. In the multivariable analysis, the disproportionally impaired D LCO was associated with worse symptoms, shorter 6-minute walking distance, paraseptal and centrilobular emphysema on computed tomography, and reduced arterial oxygen and carbon dioxide pressures compared to the reference (FEV 1 z -score>-3 and D LCO z -score>-3). In the multivariable Cox proportional hazard model, a higher long-term mortality was observed in the disproportionally impaired D LCO is common and associated with increased symptoms, emphysema, arterial blood gas abnormalities, and increased long-term mortality in patients with COPD.LCO z -score≤-3 and FEV 1 z -score≤-3 group. The disproportionally impaired D LCO relative to FEV 1 is common and associated with increased symptoms, emphysema, arterial blood gas abnormalities, and increased long-term mortality in patients with COPD.

Background: Previous analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbations (AE) of CPFE., Methods: We retrospectively reviewed the medical records of patients who had been treated at the Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan-Meier method., Results: Treatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/μL; white blood cell count: 8810 /μL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/μL, p < 0.001; white blood cells: 10809/μL, p = 0.0096). The baseline Gender-Age-Physiology scores were not significantly different between the two groups (CPFE, 4.5 points; IPF, 4.7 points; p = 0.58). Kaplan-Meier curves revealed that the survival time after AE for patients with CPFE was longer than that for patients with IPF (p < 0.001, log-rank test)., Conclusions: Survival prognoses after AE were significantly better for patients with CPFE than that for those with IPF. Our findings may improve the medical treatment and respiratory management of patients with AE-CPFE.

Background: Different characteristics of patients with chronic obstructive pulmonary disease (COPD) between Western and Japanese populations have been reported. Risk factors for COPD exacerbation have been reported in Western countries but have not been studied in Japan., Patients and methods: We retrospectively examined risk factors for COPD exacerbation. A total of 156 Japanese patients were enrolled, and the records of 136 patients were analyzed., Results: In the exacerbation group (n=60), body mass index, forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ), the FEV 1 /FVC ratio (FEV 1 /FVC), the percent predicted values of FEV 1 (%FEV 1 ), and serum total protein (TP) and albumin concentrations were lower, and age, mortality rate, frequency of common cold and pneumonia, COPD severity rankings, modified Medical Research Council (mMRC) dyspnea score, and proportions of patients with severe emphysema (>50% of low attenuation area) and receiving long-term oxygen therapy were higher than those in the nonexacerbation group (n=76). However, the proportion of patients with a greater number of eosinophils (≥200/μL and/or ≥2%) and the exhaled nitric oxide concentration did not differ between the two groups. In the univariate analysis, the risk factors for exacerbation were age; long-term oxygen therapy; low FVC, FEV 1 , FEV 1 /FVC and %FEV 1 ; high COPD severity ranking and mMRC score; severe emphysema; hypoproteinemia (<6.5 g/dL); hypoalbuminemia (<3.5 g/dL); leukocytosis; lymphocytopenia; and anemia. In the multivariate analysis, the risk factors were hypoalbuminemia, hypoproteinemia and low FEV 1 . Additionally, in patients in the exacerbation-induced mortality subgroup, age, exacerbation frequency, mMRC score and the proportion of patients with lymphocytopenia were higher, and FVC, %FVC, FEV 1 , serum TP concentration and the lymphocyte number were lower than those in the exacerbation survival subgroup., Conclusion: Malnutrition, airflow limitation and severe emphysema were risks for exacerbation and mortality associated with infection in Japanese patients with COPD., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Yamaya et al.)

Background: Fractal dimension ( D ) characterises the size distribution of low attenuation clusters on CT and assesses the spatial heterogeneity of emphysema that per cent low attenuation volume (%LAV) cannot detect. This study tested the hypothesis that %LAV and D have different roles in predicting decline in FEV 1 , exacerbation and mortality in patients with COPD., Methods: Chest inspiratory CT scans in the baseline and longitudinal follow-up records for FEV 1 , exacerbation and mortality prospectively collected over 10 years in the Hokkaido COPD Cohort Study were examined (n=96). The associations between CT measures and long-term outcomes were replicated in the Kyoto University cohort (n=130)., Results: In the Hokkaido COPD cohort, higher %LAV, but not D , was associated with a greater decline in FEV 1 and 10-year mortality, whereas lower D , but not %LAV, was associated with shorter time to first exacerbation. Multivariable analysis for the Kyoto University cohort confirmed that lower D at baseline was independently associated with shorter time to first exacerbation and that higher LAV% was independently associated with increased mortality after adjusting for age, height, weight, FEV 1 and smoking status., Conclusion: These well-established cohorts clarify the different prognostic roles of %LAV and D , whereby lower D is associated with a higher risk of exacerbation and higher %LAV is associated with a rapid decline in lung function and long-term mortality. Combination of %LAV and fractal D may identify COPD subgroups at high risk of a poor clinical outcome more sensitively., Competing Interests: Competing interests: The Hokkaido COPD Cohort Study is supported by a scientific research grant to the Hokkaido COPD Cohort Study from the Ministry of Education, Science, Culture and Sports of Japan (17390239 and 2139053 to MN), Nippon Boehringer Ingelheim, Pfizer, and a grant to the Respiratory Failure Research Group from the Ministry of Health, Labour and Welfare, Japan. MS reports grants from GlaxoSmithKline, grants from Novartis and grants from AstraZeneca outside the current work. None of these companies had a role in the design or analysis of the study or in the writing of the manuscript. The Kyoto University Cohort Study was supported by the Japan Society for the Promotion of Science (JSPS) (No 16390234, No 21590964 and No 17H06807) and a grant to the Respiratory Failure Research Group from the Ministry of Health, Labour and Welfare, Japan. NT, SS and TH report a grant from Fujifilm Medical outside the current work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood., Methods: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined., Results: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers., Conclusion: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.

Background: The presence of emphysema on computed tomography (CT) is associated with an increased frequency of lung cancer, but the postoperative outcomes of patients with pulmonary emphysema are not well known. The objective of this study was to investigate the association between the extent of emphysema and long-term outcomes, as well as mortality and postoperative complications, in early-stage lung cancer patients after pulmonary resection., Methods: The clinical records of 566 consecutive lung cancer patients who underwent pulmonary resection in our department were retrospectively reviewed. Among these, the data sets of 364 pathological stage I patients were available. The associations between the extent of lung emphysema and long-term outcomes and postoperative complications were investigated. Emphysema was assessed on the basis of semiquantitative CT. Surgery-related complications of Grade ≥ II according to the Clavien-Dindo classification were included in this study., Results: Emphysema was present in 63 patients. The overall survival and relapse-free survival of the non-emphysema and emphysema groups at 5 years were 89.0 and 61.3% (P < 0.001), respectively, and 81.0 and 51.7%, respectively (P < 0.001). On multivariate analysis, significant prognostic factors were emphysema, higher smoking index, and higher histologic grade (p < 0.05). Significant risk factors for poor recurrence-free survival were emphysema, higher smoking index, higher histologic grade, and presence of pleural invasion (P < 0.05). Regarding Grade ≥ II postoperative complications, pneumonia and supraventricular tachycardia were more frequent in the emphysema group than in the non-emphysema group (P = 0.003 and P = 0.021, respectively)., Conclusion: The presence of emphysema affects the long-term outcomes and the development of postoperative complications in early-stage lung cancer patients.

Background: During the last decade it has been clarified that the inhalation of indium compounds can evoke alveolar proteinosis, cholesterol granuloma, pulmonary fibrosis and emphysema. In this study, we aimed to elucidate the characteristics and time course of pulmonary disorders among indium workers using comprehensive pulmonary examinations at an indium-processing factory., Methods: Data for 84 male workers who underwent the examinations for nine consecutive years from 2002 to 2010 were analysed regarding their symptoms, serum indium concentration (sIn), serum markers of interstitial pneumonia, pulmonary function test parameters and high-resolution CT (HRCT) findings of the lungs., Results: In association with improvements in the work environment and work practice, the sIn levels decreased with significant reductions in the KL-6 and surfactant protein D (SP-D) levels. Regarding the HRCT findings, the interstitial lesions regressed partially, whereas emphysematous lesions increased progressively in the workers with high sIn values. FEV1/FVC decreased with the years and the rate of decrease was significantly greater in those with high sIn. The biological half-life of sIn was estimated to be 8.09 years., Conclusions: The present findings suggest that the sIn, SP-D, KL-6 levels and radiological interstitial changes can be reduced in indium workers by alleviating exposure to indium, whereas emphysematous lesions can progress among those with a history of heavy exposure., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Objective: Vitamin D supplementation can decrease the vulnerability to pulmonary infections. Therefore, it is speculated that the genes related to vitamin D metabolism are associated with an exacerbation-prone phenotype in chronic obstructive pulmonary disease (COPD). Because genetic variations of group component (GC) affect immunological capacity and serum vitamin D concentration, they could also affect the susceptibility to COPD exacerbation and the disease progression. We investigated the association between GC genetic variations and COPD and its exacerbation frequency in a Japanese population., Methods: We performed genotype analysis of 361 COPD patients and 219 controls to identify two coding single nucleotide polymorphisms of GC, rs4588 and rs7041. We examined whether these polymorphisms were associated with the frequency of COPD exacerbation and analysed the correlation between the genotypes, COPD, emphysema severity and COPD progression, namely, the annual decline in airflow obstruction and diffusing capacity., Results: Subjects with a C allele at rs4588 exhibited a higher frequency of exacerbations (P = 0.0048), greater susceptibility to chronic obstructive pulmonary disease (P = 0.0003), and emphysema (P = 0.0029), and a tendency for rapid decline of airflow obstruction (P = 0.0927)., Conclusions: GC variations may affect exacerbation susceptibility, possibly leading to COPD worsening and its progression., (© 2014 The Authors. Respirology © 2014 Asian Pacific Society of Respirology.)

Background: The purpose of this study was to clarify the association between morphological phenotypes according to the predominance of emphysema and efficacy of long-acting muscarinic antagonist and β(2) agonist bronchodilators in patients with chronic obstructive pulmonary disease (COPD)., Methods: Seventy-two patients with stable COPD treated with tiotropium (n = 41) or salmeterol (n = 31) were evaluated for pulmonary function, dynamic hyperinflation following metronome-paced incremental hyperventilation, six-minute walking distance, and St George's Respiratory Questionnaire (SGRQ) before and 2-3 months following treatment with tiotropium or salmeterol. They were then visually divided into an emphysema dominant phenotype (n = 25 in the tiotropium-treated group and n = 22 in the salmeterol-treated group) and an emphysema nondominant phenotype on high-resolution computed tomography, and the efficacy of the two drugs in each phenotype was retrospectively analyzed., Results: Tiotropium significantly improved airflow limitation, oxygenation, and respiratory impedance in both the emphysema dominant and emphysema nondominant phenotypes, and improved dynamic hyperinflation, exercise capacity, and SGRQ in the emphysema dominant phenotype but not in the emphysema nondominant phenotype. Salmeterol significantly improved total score for SGRQ in the emphysema phenotype, but no significant effects on other parameters were found for either of the phenotypes., Conclusion: These findings suggest that tiotropium is more effective than salmeterol for airflow limitation regardless of emphysema dominance, and also can improve dynamic hyperinflation in the emphysema dominant phenotype, which results in further improvement of exercise capacity and health-related quality of life.