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Background: Expiratory flow limitation (EFL) during tidal breathing and lung hyperinflation have been identified as major decisive factors for disease status, prognosis and response to therapy in obstructive lung diseases. Aim: To investigate the delta values between expiratory and inspiratory resistance and reactance, measured using respiratory oscillometry and its correlation with air trapping and symptoms in subjects with obstructive lung diseases. Methods: Four hundred and seventy‐one subjects (96 with chronic obstructive pulmonary disease [COPD], 311 with asthma, 30 healthy smokers and 34 healthy subjects) were included. Spirometry, body plethysmography and respiratory oscillometry measurements were performed and the differences between the expiratory and inspiratory respiratory oscillometry values (as delta values) were calculated. Questionnaires regarding symptoms and quality of life were administered. Results: Patients with COPD and healthy smokers had an increased delta resistance at 5 Hz (R5) compared with patients with asthma (p < 0.0001 and p = 0.037, respectively) and healthy subjects (p = 0.0004 and p = 0.012, respectively). Patients with COPD also had higher values of ΔR5–R19 than healthy subjects (p = 0.0001) and patients with asthma (p < 0.0001). Delta reactance at 5 Hz (X5) was significantly more impaired in COPD patients than in asthma and healthy subjects (p < 0.0001 for all). There was a correlation between the ratio of residual volume and total lung capacity and ΔR5 (p = 0.0047; r = 0.32), ΔR5–R19 (p = 0.0002; r = 0.41) and ΔX5 (p < 0.0001; r = −0.44), for all subjects. ΔX5 correlated with symptoms in COPD, healthy smokers and patients with asthma. In addition, ΔR5 correlated with asthma symptoms. Conclusion: EFL was most prominent in parameters measuring peripheral resistance and reactance and correlated with air trapping and airway symptoms. [ABSTRACT FROM AUTHOR]

Rationale: Preserved ratio impaired spirometry (PRISm) is a recently recognized spirometric pattern defined by a ratio of forced expiratory volume in 1 second to forced vital capacity of at least 0.70 and a forced expiratory volume in 1 second  <80% of reference. For unclear reasons, PRISm is associated with increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is a major mechanism of CV disease, which can be measured by carotid-femoral pulse-wave velocity (cfPWV). Objectives: We explored the hypothesis that cfPWV would be increased in individuals with PRISm and airflow limitation (AL). Methods: We measured forced spirometry, lung volumes by body plethysmography, and cfPWV in 9,466 subjects recruited from the general population in the Austrian cross-sectional LEAD (Lung, Heart, Social, Body) study and tested the association of arterial stiffness with PRISm and AL by multivariable linear regression analysis. Individuals younger than 18 years were excluded from the study. Results: Individuals with PRISm (n = 431; 4.6%) were of similar age to those with normal spirometry (n = 8,136; 85.9%) and significantly younger than those with AL (n = 899; 9.5%). Arterial hypertension, diabetes mellitus, coronary artery disease, heart failure, and peripheral arterial occlusive disease were significantly more common in individuals with PRISm than in those with normal lung function and similar to those with AL. There was a significant association between PRISm and arterial stiffness on bivariate linear regression analysis (crude model, β = 0.038; 95% confidence interval [CI], 0.016–0.058), which persisted after robust adjustment for clinical confounders upon multivariable analysis (final model, β = 0.017; 95% CI, 0.001–0.032). cfPWV was significantly higher in individuals with PRISm irrespective of the presence of established CV disease or pulmonary restriction. AL also showed a significant association with arterial stiffness on multivariable linear regression analysis (final model, β = 0.025; 95% CI, 0.009–0.042). Conclusions: Arterial stiffness measured by cfPWV is increased in individuals with PRISm independent of CV disease and risk factors. The pathobiological mechanisms underlying this association deserve further research. [ABSTRACT FROM AUTHOR]

Abstract Introduction Chronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients. Aim To evaluate in peripheral lung of COPD patients, the expression of some of the less investigated key components of the innate immune responses leading to IFN productions including: IFN-receptors (IFNAR1/IFNAR2), IRF-3 and MDA-5. Correlations with clinical traits and with the inflammatory cell profile have been assessed. Methods Lung specimens were collected from 58 subjects undergoing thoracic surgery: 22 COPD patients, 21 smokers with normal lung function (SC) and 15 non-smoker controls (nSC). The expression of IFNAR1, IFNAR2, IRF-3 and MDA-5, of eosinophils and activated NK cells (NKp46+) were quantified in the peripheral lung by immunohistochemistry. Results A significant increase of IRF-3 + alveolar macrophages were observed in COPD and SC compared with nSC subjects. However, in COPD patients, the lower the levels of IRF-3 + alveolar macrophages the lower the FEV1 and the higher the exacerbation rate. The presence of chronic bronchitis (CB) was also associated with low levels of IRF-3 + alveolar macrophages. NKp46 + cells, but not eosinophils, were increased in COPD patients compared to nSC patients (p

Abstract Background Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder affecting 9–25% of the general adult population. Aim To assess airflow limitation by spirometric indices in patients with obstructive sleep apnea. Patients and methods This observational case–control study was conducted on 60 subjects who were divided into four groups: Group I (control group), included 20 subjects chosen from other departments, who had no respiratory complaints with apnea–hypopnea index (AHI

Kazuhiko Watanabe,1,2 Hisamitsu Omori,3 Ayumi Onoue,3 Kenichi Kubota,4 Minoru Yoshida,4 Takahiko Katoh1 1Department of Public Health, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 2Center for Research of the Aging Workforce, University of Occupational and Environmental Health, Fukuoka, Japan; 3Department of Laboratory Sciences in Environmental Hygiene and Public Health, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 4Japanese Red Cross Kumamoto Health Care Center, Kumamoto, JapanCorrespondence: Hisamitsu Omori, Department of Laboratory Sciences in Environmental Hygiene and Public Health, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan, Tel/Fax +81-96-373-5462, Email omorih@gpo.kumamoto-u.ac.jpPurpose: This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women.Participants and Methods: This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (− 4 to − 1), or high (

Introduction: Chronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients. Aim: To evaluate in peripheral lung of COPD patients, the expression of some of the less investigated key components of the innate immune responses leading to IFN productions including: IFN-receptors (IFNAR1/IFNAR2), IRF-3 and MDA-5. Correlations with clinical traits and with the inflammatory cell profile have been assessed. Methods: Lung specimens were collected from 58 subjects undergoing thoracic surgery: 22 COPD patients, 21 smokers with normal lung function (SC) and 15 non-smoker controls (nSC). The expression of IFNAR1, IFNAR2, IRF-3 and MDA-5, of eosinophils and activated NK cells (NKp46+) were quantified in the peripheral lung by immunohistochemistry. Results: A significant increase of IRF-3 + alveolar macrophages were observed in COPD and SC compared with nSC subjects. However, in COPD patients, the lower the levels of IRF-3 + alveolar macrophages the lower the FEV1 and the higher the exacerbation rate. The presence of chronic bronchitis (CB) was also associated with low levels of IRF-3 + alveolar macrophages. NKp46 + cells, but not eosinophils, were increased in COPD patients compared to nSC patients (p < 0.0001). Conclusions: Smoking is associated with higher levels of innate immune response as showed by higher levels of IRF-3 + alveolar macrophages and NKp46 + cells. In COPD, exacerbation rates, severe airflow obstruction and CB were associated with lower levels of IRF-3 expression, suggesting that innate immune responses characterize specific clinical traits of the disease. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder affecting 9–25% of the general adult population. Aim: To assess airflow limitation by spirometric indices in patients with obstructive sleep apnea. Patients and methods: This observational case–control study was conducted on 60 subjects who were divided into four groups: Group I (control group), included 20 subjects chosen from other departments, who had no respiratory complaints with apnea–hypopnea index (AHI < 5); Group II (mild group), included 11 patients with mild sleep apnea, 5 ≤ AHI < 15; Group III (moderate group), included 17 patients with moderate sleep apnea, 15 ≤ AHI < 30; and Group IV (severe group), included 12 patients with severe sleep apnea, AHI ≥ 30 at the Chest Department, Faculty of Medicine, Helwan University, from August 2021 until June 2022. Results: There was no statistically significant relation found between the severity of AHI and all the previous pulmonary function parameters except a statistically significant decrease in FEF (25–75%) in the moderate group than the mild group and also in the severe group than the moderate group (p-value < 0.001). There was a statistically significant positive correlation found between AHI and BMI and NC and a negative correlation found between AHI and FEF (25–75%) while no statistically significant correlation was found between AHI and the other studied parameters. Conclusion: Obstructive sleep apnea (OSA) is associated with airflow limitation by spirometric indices, although this association is statistically insignificant. On the other hand, the severity of obstructive sleep apnea is directly proportional to the seriousness of the apnea–hypopnea index (AHI). Strong correlations were found between the severity of AHI and body mass index (BMI), neck circumference, and FEF (25–75%). [ABSTRACT FROM AUTHOR]

[Display omitted] Airflow limitation is a hallmark of chronic obstructive pulmonary disease, which can develop through different lung function trajectories across the life span. There is a need for longitudinal studies aimed at identifying circulating biomarkers of airflow limitation across different stages of life. This study sought to identify a signature of serum proteins associated with airflow limitation and evaluate their relation to lung function longitudinally in adults and children. This study used data from 3 adult cohorts (TESAOD [Tucson Epidemiological Study of Airway Obstructive Disease], SAPALDIA [Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults], LSC [Lovelace Smoker Cohort]) and 1 birth cohort (TCRS [Tucson Children's Respiratory Study]) (N = 1940). In TESAOD, among 46 circulating proteins, we identified those associated with FEV 1 /forced vital capacity (FVC) percent (%) predicted levels and generated a score based on the sum of their z -scores. Cross-sectional analyses were used to test the score for association with concomitant lung function. Longitudinal analyses were used to test the score for association with subsequent lung function growth in childhood and decline in adult life. After false discovery rate adjustment, serum levels of 5 proteins (HP, carcinoembryonic antigen, ICAM1, CRP, TIMP1) were associated with percent predicted levels of FEV 1 /FVC and FEV 1 in TESAOD. In cross-sectional multivariate analyses the 5-biomarker score was associated with FEV 1 % predicted in all adult cohorts (meta-analyzed FEV 1 decrease for 1-SD score increase: −2.9%; 95% CI: −3.9%, −1.9%; P = 2.4 × 10−16). In multivariate longitudinal analyses, the biomarker score at 6 years of age was inversely associated with FEV 1 and FEV 1 /FVC levels attained by young adult life (P =.02 and.005, respectively). In adults, persistently high levels of the biomarker score were associated with subsequent accelerated decline of FEV 1 and FEV 1 /FVC (P =.01 and.001). A signature of 5 circulating biomarkers of airflow limitation was associated with both impaired lung function growth in childhood and accelerated lung function decline in adult life, indicating that these proteins may be involved in multiple lung function trajectories leading to chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to determine the incidence rate, pathogen composition, and risk factors, particularly airflow limitation, associated with bacterial respiratory infection and pneumonia in a prospective cohort of well-treated people with HIV (PWH) between 2015-2021. Methods: We included 1007 PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Spirometry was performed at inclusion. Microbiology samples were collected prospectively. Cumulative incidence was determined by the Aalen-Johansen estimator. Cox proportional hazard models were used to calculate risk factors, adjusted for traditional and HIV-specific variables. Results: The incidence rates of first bacterial respiratory infection and pneumonia were 12.4 (95% CI 9.7-15.5) and 5.5 (95% CI: 3.8-7.7) per 1000 person-years, respectively. The cumulative incidence of pneumonia was four times higher in PWH with airflow limitation (11.8% vs 3.2%, P

Aldo Pezzuto,1 Alberto Ricci,1 Michela D’Ascanio,1 Alba Moretta,1 Giuseppe Tonini,2 Noemi Calabrò,1 Valeria Minoia,1 Alessia Pacini,1 Giuliana De Paolis,1 Eleonora Chichi,1 Elisabetta Carico,3 Antonella Tammaro4 1Department of Cardiovascular and Respiratory Sciences, S Andrea Hospital, Sapienza University, Rome, Italy; 2Oncology Department, Campus Bio-Medico University, Rome, Italy; 3Clinical and Molecular Medicine Department, S Andrea Hospital, Sapienza University, Rome, Italy; 4Department of Neuroscience- NESMOS, S.Andrea Hospital, Sapienza University, Rome, ItalyCorrespondence: Aldo Pezzuto, Email aldo.pezzuto@uniroma1.itBackground: Cigarette smoke exposure is the main preventable cause of chronic obstructive pulmonary disease (COPD). Airflow limitation is closely associated with smoking exposure. Smoking could also interfere with lipid metabolism.Aim: To determine the respiratory functional and metabolic changes after smoking cessation in smokers in the short term.Methods: All patients were current smokers. They were assessed by spirometry and questionnaires such as COPD assessment test(CAT), modified Medical Research Council (mMRC) test for dyspnea, Fagestrom’s test for nicotine dependence. Exhaled CO was detected in order to evaluate smoking exposure and smoking cessation (normal value< 7 ppm). A blood sampling was eventually taken for vitamin D and cholesterol assay. All patients underwent therapy with counselling and varenicline as first-line treatment according to its schedule. Detection time: at baseline and one month after smoking cessation.Results: All patients quit smoking during treatment. The mean age was 62 with a prevalence of males. The analysis revealed the following mean values at baseline: CAT mean score was 15, pack-years 35.5, Fagestrom’s Test mean score 5.0. The West’s value was 8.5, whereas Body mass index (BMI) was 25.5.Cigarette daily consumption mean value was 22.5. The comparison before and at follow up one month after smoking cessation about functional and metabolic parameters, show us the following results: FEV 1 was increased by 200 mL (p< 0.02), FEF 25/75 was improved as well as mMRC test. The eCO was dropped to as low as 8 ppM. Interestingly the vitamin D level was increased from 25 to 28 ng/mL without any support therapy. The cholesterol total level was reduced and CAT value and DLCO were also significantly improved.Conclusion: Quit smoking is useful to improve symptoms, respiratory function and metabolic parameters in the short term.Keywords: airflow limitation, smoking cessation, lipid metabolism

• We studied bacterial respiratory infections and pneumonia in people with HIV (PWH). • The cumulative incidence of pneumonia was highest in PWH with airflow limitation. • PWH with active smoking had a higher risk of bacterial infections and pneumonia. • PWH with previous AIDS had a higher risk of bacterial respiratory infections. We aimed to determine the incidence rate, pathogen composition, and risk factors, particularly airflow limitation, associated with bacterial respiratory infection and pneumonia in a prospective cohort of well-treated people with HIV (PWH) between 2015-2021. We included 1007 PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Spirometry was performed at inclusion. Microbiology samples were collected prospectively. Cumulative incidence was determined by the Aalen-Johansen estimator. Cox proportional hazard models were used to calculate risk factors, adjusted for traditional and HIV-specific variables. The incidence rates of first bacterial respiratory infection and pneumonia were 12.4 (95% CI 9.7-15.5) and 5.5 (95% CI: 3.8-7.7) per 1000 person-years, respectively. The cumulative incidence of pneumonia was four times higher in PWH with airflow limitation (11.8% vs 3.2%, P <0.001). Risk factors for bacterial respiratory infection were airflow limitation (hazard ratio [HR] 2.9, [95% CI: 1.7-5.1], P <0.001), smoking (HR 2.3, [95% CI: 1.4-3.8], P <0.001), and previous AIDS-defining event (HR 2.0, [95% CI: 1.2-3.3], P = 0.009). For pneumonia, airflow limitation (HR 2.7, [95% CI: 1.2-6.3], P = 0.016), smoking (HR 2.5, [95% CI: 1.2-5.4], P = 0.016), and older age (HR 1.5, [95% CI: 1.1-2.1], P = 0.015) were identified as risk factors. Increased emphasis on airflow limitation prevention, including smoking cessation, may reduce the burden of bacterial respiratory infection and pneumonia in PWH. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large‐scale prospective UK Biobank cohort. Materials and Methods: Our approach comprised a cross‐sectional study and a prospective cohort. Periodontal diseases were determined based on the participants' self‐reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross‐sectional study and the prospective cohort, respectively. Results: The cross‐sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015–1.059). The cohort study included 379,266 participants with a median follow‐up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174–1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus. Conclusions: Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD. [ABSTRACT FROM AUTHOR]

Yijun Zhou,1 Maria R Ampon,2 Michael J Abramson,3 Alan L James,4 Graeme P Maguire,5 Richard Wood-Baker,6 David P Johns,6 Guy B Marks,1,7 Helen K Reddel,2,8,9 Brett G Toelle1,8,9 1The Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia; 2Australian Centre for Airways Disease Monitoring, The Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia; 3School of Public Health & Preventive Medicine, Monash University, Melbourne, VIC, Australia; 4Sir Charles Gairdner Hospital, Perth, WA, Australia; 5Curtin Medical School, Curtin University, Perth, WA, Australia; 6Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; 7South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia; 8Faculty of Medicine, Health and Human Science, Macquarie University, Sydney, NSW, Australia; 9Sydney Local Health District, Sydney, NSW, AustraliaCorrespondence: Brett G Toelle, Woolcock Institute of Medical Research, 431 Glebe Point Road, Glebe, NSW, 2037, Australia, Email brett.toelle@woolcock.org.auPurpose: Population data on the burden of chronic obstructive pulmonary disease (COPD) are often based on patient-reported diagnoses of COPD, emphysema or chronic bronchitis, without spirometry. We aimed to investigate the relationship between health burden, quality of life and severity of airway obstruction in Australian adults aged ≥ 40 years.Methods: We used data from the BOLD Australia study, which included randomly selected adults aged ≥ 40 years from six study sites to reflect the sociodemographic and geographic diversity of the Australian population (n = 3522). Participants with post-bronchodilator airflow limitation (ratio of forced expiratory volume in 1 second FEV1 to forced vital capacity < 0.7) were grouped by GOLD spirometry grades 1– 4. Quality of life was assessed with Short Form 12 (SF-12) Health Survey Questionnaire. Health burden was assessed as lost time off work or social activities, and healthcare utilization.Results: Of the study sample, 2969 participants did not have airflow limitation, 294 (8.4%) were classified as GOLD Grade 1, 212 (6.0%) as GOLD 2 and 43 (1.2%) as GOLD 3– 4. Participants with higher GOLD grades had more respiratory symptoms, more comorbidities and greater burden than those with lower GOLD grades. The scores of mental and physical subscales of SF-12 were lower, indicating worse quality of life, from the no airflow limitation group to the GOLD 3– 4 group (P = 0.03 and P < 0.001, respectively).Conclusion: Greater airflow limitation is associated with greater burden and poor quality of life. Interventions to prevent, or reduce the level of, airflow limitation will reduce the symptom burden and improve quality of life for patients.Keywords: chronic obstructive pulmonary disease, airflow limitation, comorbidities, The Burden of Obstructive Lung Disease, quality of life

Rationale: Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objectives: To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. Methods: The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results: In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions: This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring. [ABSTRACT FROM AUTHOR]

While static mechanical forces govern resting lung volumes, dynamic forces determine tidal breathing, airflow, and changes in airflow and lung volume during normal and abnormal breathing. This section will examine the mechanisms, measurement methodology, and interpretation of the dynamic changes in airflow and lung volume that occur in health and disease. We will first examine how the total work of breathing can be described by the parameters of the equation of motion, which determine the pressure required to move air into and out of the lung. This will include a detailed description of airflow characteristics and airway resistance. Next, we will review the changes in pressure and flow that determine maximal forced inspiration and expiration, which result in the maximal flow–volume loop and the clinically important forced expired volume in 1 second. We will also assess the mechanisms and interpretation of bronchodilator responsiveness, dynamic hyperinflation, and airways hyperresponsiveness. [ABSTRACT FROM AUTHOR]

Background: Obstructive upper airway pathologies are a great clinical challenge for the airway surgeon. Protection against acute obstruction is critical, but avoidance of unnecessary tracheostomy must also be considered. Decision‐making regarding airway, although supported by some objective findings, is largely guided by subjective experience and training. This investigation aims to study the relationship between clinical respiratory distress and objective measures of airway resistance in laryngeal cancer as determined by computational fluid dynamic (CFD) and morphometric analysis. Methods: Retrospective CT and clinical data were obtained for series of 20 cases, defined as newly diagnosed laryngeal cancer patients who required admission or urgent airway surgery, and 20 controls. Cases and controls were matched based on T‐staging. Image segmentation and morphometric analysis were first performed. Computational models based on the lattice Boltzmann method were then created and used to quantify the continuous mass flow, rigid wall, and constant static pressure inlet boundary conditions. Results: The analysis demonstrated a significant relationship between airway resistance and acute obstruction (OR 1.018, 95% CI 1.001–1.045). Morphometric analysis similarly demonstrated a significant relationship when relating measurements based on the minimum cross‐section, but not on length of stenosis. Morphometric measurements also showed significance in predicting CFD results, and their relationship demonstrated that airway pressures increase exponentially below 2.5 mm. Tumor subsite did not show a significant difference, although the glottic subgroup tended to have higher resistances. Conclusion: Airway resistance analysis from CFD computation correlated with presence of acute distress requiring emergent management. Morphometric analysis showed a similar correlation, demonstrating a radiologic airway assessment technique on which future risk estimation could be performed. Level of Evidence: 4 (case–control study) Laryngoscope, 133:2734–2741, 2023 [ABSTRACT FROM AUTHOR]

Abstract Introduction Cytomegalovirus (CMV) seropositivity has been recently linked to severity and progression of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). To date, no longitudinal study has addressed the relation of CMV serology to levels and decline of lung function in the general adult population. Methods We evaluated 403 participants from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) who at enrollment were aged 28–55 years and completed lung function tests. During follow‐up, the 403 participants completed on average 7.2 lung function tests per subject for a total of 2908 observations over a mean period of 14.7 years. We tested CMV serology in serum samples from enrollment and categorized participants into low, medium, and high CMV serology based on tertiles. The relation of CMV serology at enrollment to lung function levels and decline during follow‐up was tested in multivariate random coefficients models. Results After full adjustment, participants in the highest CMV serology tertile had faster declines of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) compared with subjects in the lowest tertile (by −7.9 ml/year 95% confidence interval [−13.9 ml/year, −1.93 ml/year], and by −0.13%/year [−0.23%/year, −0.026%/year], respectively). These CMV effects were additive with those of cigarette smoking. No associations were found between CMV serology and FVC, indicating specific effects of CMV seropositivity on airflow limitation. Conclusion High CMV serology in young to mid‐adult life may be linked to increased COPD risk through an accelerated decline of lung function.

Background: The physiological importance of mucus plugs in computed tomography (CT) imaging is being increasingly recognized. However, whether airway inflammation and smoking affect the association between mucus plugs and clinical–physiological outcomes in asthma remains to be elucidated. The objective of this study is to examine how airway inflammation and/or smoking affect the correlation of CT-based mucus plug scores with exacerbation frequency and airflow limitation indices in asthma. Methods: A total of 168 patients with asthma who underwent chest CT and sputum evaluation were enrolled and classified in eosinophilic asthma (EA; n = 103) and non-eosinophilic asthma (NEA; n = 65) groups based on sputum eosinophil percentage (cut-off: 3%). The mucus plug score was defined as the number of lung segments with mucus plugs seen on CT. Results: More mucus plugs were detected on CT scans in the EA group than in the NEA group, regardless of smoking status. Mucus plug score and exacerbation frequency during one year after enrollment were significantly associated in the EA group but not in the NEA group after adjusting for demographics, blood eosinophil count, and fractional exhaled nitric oxide. Mucus plug score was associated with percentage of predicted forced expiratory volume in 1 s in non-smoking individuals in the EA and NEA group and in smoking individuals in the EA group but not in the NEA group after adjusting for demographics. Conclusions: The association of mucus plug score with exacerbation frequency and reduced lung function may vary due to airway inflammatory profile and smoking status in asthma.

Abstract Background Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations. Methods In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed. Results COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p

Background: Observational studies showed associations between smoking, and airflow limitation, with lung squamous cell carcinoma (LUSC). However, the causal association of airflow limitation with LUSC and the modification by smoking status for the association remains unclear. Methods: Genetic summary data were obtained from large genome-wide association studies (GWAS). One hundred two single nucleotide polymorphisms (SNPs) for airflow limitation (i.e., FEV1/FVC < 0.7) and 153 SNPs for smoking behavior were used as instrumental variables and the main MR analysis methods. The univariable and multivariable Mendelian Randomization (MR) in a two-sample setting were performed to assess the association of airflow limitation, and smoking behavior with LUSC. Results: In the univariable MR analysis, genetic predisposition towards airflow limitation [Inverse Variance-Weighted (IVW) method Odds Ratio (OR) = 4.83, 95% Confidence Interval (CI) 1.55 to 15.06, P = 0.006], age of smoking initiation (IVW method OR = 0.10, 95%CI 0.02 to 0.36, P < 0.001), cigarettes smoked per day (IVW method OR = 3.10, 95%CI 2.07 to 4.63, P < 0.001), ex-smoking (IVW method OR = 0.47, 95%CI 0.31 to 0.69, P < 0.001), current smoking status (IVW method OR = 13.08, 95%CI 2.53 to 67.84, P = 0.002), pack-years of smoking (Weighted median method OR = 11.49, 95%CI 3.71 to 35.63, P < 0.001) were associated with LUSC. In the multivariable MR analysis, the causal effect of airflow limitation was still observed on LUSC (IVW method OR = 2.97, 95% CI 1.09 to 8.04, P = 0.032 adjusted for age of smoking initiation and cigarettes smoked per day; IVW method OR = 3.24, 95% CI 1.09 to 9.58, P = 0.033 adjusted for ex-smoking, current smoking status, and pack years of smoking; IVW method OR = 2.91, 95% CI 1.01 to 8.41, P = 0.049 adjusted for 5 smoking behaviors mentioned above). Conclusions: Our MR analysis demonstrated that airflow limitation is likely to be an independent predictor of LUSC. [ABSTRACT FROM AUTHOR]

Lütfiye Kiliç,1 Seda Tural Önür,2 Aslı Gorek Dilektasli,3 Gaye Ulubay,4 Arif Balcı5 1Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Pulmonologist, Department of Pulmonary Rehabilitation, University of Health Sciences, Istanbul, Turkey; 2Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Associate Professor, Department of Chest Diseases, University of Health Sciences, Istanbul, Turkey; 3Uludağ University, Faculty of Medicine, Associate professor, Department of Chest Diseases, Bursa, Turkey; 4Başkent University, Faculty of Medicine, Professor, Department of Chest Diseases, Ankara, Turkey; 5Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Physiotherapist, Department of Pulmonary Rehabilitation, University of Health Sciences, Istanbul, TurkeyCorrespondence: Lütfiye Kiliç, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey, Tel +90 532 397 7172, Email lutuf1@yahoo.comPurpose: We investigated the effect of pulmonary rehabilitation (PR) on airway resistance in chronic obstructive pulmonary disease (COPD) patients with severe airway obstruction and hyperinflation.Patients and Methods: This retrospective cohort study was conducted with data from severe COPD cases with those who underwent an 8-week PR program. Main inclusion criteria were having severe airflow obstruction (defined as a forced expiratory volume in one second (FEV1) < 50%) and plethysmographic evaluation findings being compatible with hyperinflation supporting the diagnosis of emphysema (presence of hyperinflation defined as functional residual capacity ratio of residual volume to total lung capacity (RV/TLC) > 120%). Primary outcomes were airway resistance (Raw) and airway conductance (Gaw) which were measured by body plethysmography, and other measurements were performed, including 6-minute walk test (6-MWT), modified Medical Research Council dyspnea scale (mMRC) and COPD assessment test (CAT).Results: Twenty-six severe and very severe COPD patients (FEV1, 35.0 ± 13.1%; RV/TLC, 163.5 ± 29.4) were included in the analyses, mean age 62.6 ± 5.8 years and 88.5% males. Following rehabilitation, significant improvements in total specific airway resistance percentage (sRawtot%, p = 0.040) and total specific airway conductance percentage (sGawtot%; p = 0.010) were observed. The post-rehabilitation mMRC scores and CAT values were significantly decreased compared to baseline results (p < 0.001 and p < 0.001, respectively). Although there were significant improvements in 6-MWT value (p < 0.001), exercise desaturation (ΔSaO2, p = 0.026), the changes in measured lung capacity and volume values were not significant.Conclusion: We concluded that PR may have a positive effect on airway resistance and airway conductance in COPD patients with severe airflow obstruction.Keywords: airway resistance, body plethysmography, airflow limitation, emphysema, lung mechanics

Guoyan Tang,1,&ast; Fengyan Wang,1,&ast; Zhenyu Liang,1,&ast; Cuixia Liang,2,&ast; Jinling Wang,3,&ast; Yuqiong Yang,1 Wanyi Tang,1,4 Weijuan Shi,1 Guoqiang Tang,3 Kai Yang,5 Zihui Wang,1 Qiasheng Li,1 Hualin Li,1 Jiaxuan Xu,1 Deyan Chen,2 Rongchang Chen5 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Neusoft Medical Systems Co., Ltd, Shenyang, People’s Republic of China; 3Qingyuan Chronic Disease Prevention Hospital, Qingyuan Occupational Disease Prevention Hospital, Qingyuan, People’s Republic of China; 4Qingyuan People’s Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchang Chen, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, People’s Republic of China, Email chenrc@vip.163.com Zhenyu Liang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email 490458234@qq.comBackground: Pulmonary vascular alteration is an important feature of chronic obstructive pulmonary disease (COPD), which is characterized by distal pulmonary vascular pruning in angiography. We aimed to further investigate the clinical relevance of pulmonary vasculature in COPD patients using non-contrast computed tomography (CT).Methods: Seventy-one control subjects and 216 COPD patients completed the questionnaires, spirometry, and computed tomography (CT) scans within 1 month and were included in the study. Small pulmonary vessels represented by percentage of cross-sectional area of pulmonary vessels smaller than 5 mm2 or 5– 10 mm2 to the total lung fields (%CSA< 5 or %CSA5– 10, respectively) were measured using ImageJ software. Spearman correlation was used to investigate the relationship between %CSA< 5 and airflow limitation. A receiver operating characteristic (ROC) curve was built to evaluate the value of %CSA< 5 in discriminating COPD patients from healthy control subjects. Segmented regression was used to analyze the relationship between %CSA< 5 and %LAA-950 (percentage of low-attenuation areas less than − 950 HU).Results: We found a significant correlation between %CSA< 5 and forced expiratory volume in one second (FEV1) percentage of predicted value (%pred) (r = 0.564, P < 0.001). The area under the ROC curve for the value of %CSA< 5 in distinguishing COPD was 0.816, with a cut-off value of 0.537 (Youden index J, 0.501; sensitivity, 78.24%; specificity, 71.83%). Since the relationship between %CSA< 5 and %LAA-950 was not constant, performance of segmented regression was better than ordinary linear regression (adjusted R2, 0.474 vs 0.332, P < 0.001 and P < 0.001, respectively). As %CSA< 5 decreased, %LAA-950 slightly increased until an inflection point (%CSA< 5 = 0.524) was reached, after which the %LAA-950 increased apparently with a decrease in %CSA< 5.Conclusion: %CSA< 5 was significantly correlated with both airflow limitation and emphysema, and we identified an inflection point for the relationship between %CSA< 5 and %LAA-950.Keywords: computed tomography, pulmonary vascular pruning, airflow limitation, emphysema, chronic obstructive pulmonary disease

Dafei Wei1 &ast;, Qi Wang2 &ast;, Shasha Liu,2 Xiaowu Tan,2 Lin Chen,2 Rongfang Tu,2 Qing Liu,2 Yuanhang Jia,2 Sha Liu2 1Department of Pediatrics, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sha Liu, Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People’s Republic of China, Email 2018020001@usc.edu.cnObjective: To explore the clinical effects of different forced expiratory volume in 1s (FEV1) reference equations on chronic obstructive pulmonary disease (COPD) airflow limitation (AFL) classification.Methods: We conducted a COPD screening program for residents over 40 years old from 2019 to 2021. All residents received the COPD screening questionnaire (COPD-SQ) and spirometry. Postbronchodilator FEV1/FVC (forced vital capacity) < 0.7 was used as the diagnostic criterion of COPD and two reference equations of FEV1 predicted values were used for AFL severity classification: the European Respiratory Society Global Lung Function Initiative reference equation in 2012 (GLI-2012) and the Guangzhou Institute of Respiratory Health reference equation in 2017 (GIRH-2017). Clinical characteristics of patients in GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease) 1– 4 grades classified by the two reference equations were compared.Results: Among 3524 participants, 659 subjects obtained a COPD-SQ score of 16 or more and 743 participants were found to have AFL. The COPD-SQ showed high sensitivity (59%) and specificity (91%) in primary COPD screening. Great differences in COPD severity classification were found when applying the two equations (p < 0.001). Compared with GIRH-2017, patients with AFL classified by GLI-2012 equations were significantly severer. The relationship between symptom scores, acute exacerbation (AE) history distributions and COPD severities classified by the two equations showed a consistent trend of positive but weak correlation. Group A, B, C and D existed in all GOLD 1 to 3 COPD patients, but in GOLD 4, only Groups B and D existed. However, no clear significant differences were found in symptoms, AE risk assessments, risk factors exposure and even the combined ABCD grouping under the two equations.Conclusion: There were significant differences in COPD AFL severity classification with GLI-2012 and GIRH-2017 FEV1 reference equations. But these severity estimation differences did not affect symptoms, AE risk assessments and ABCD grouping of patients at all GOLD grades.Keywords: COPD, airflow limitation, FEV1%pred, symptoms assessment, acute exacerbation

Introduction: Cytomegalovirus (CMV) seropositivity has been recently linked to severity and progression of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). To date, no longitudinal study has addressed the relation of CMV serology to levels and decline of lung function in the general adult population. Methods: We evaluated 403 participants from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) who at enrollment were aged 28–55 years and completed lung function tests. During follow‐up, the 403 participants completed on average 7.2 lung function tests per subject for a total of 2908 observations over a mean period of 14.7 years. We tested CMV serology in serum samples from enrollment and categorized participants into low, medium, and high CMV serology based on tertiles. The relation of CMV serology at enrollment to lung function levels and decline during follow‐up was tested in multivariate random coefficients models. Results: After full adjustment, participants in the highest CMV serology tertile had faster declines of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) compared with subjects in the lowest tertile (by −7.9 ml/year 95% confidence interval [−13.9 ml/year, −1.93 ml/year], and by −0.13%/year [−0.23%/year, −0.026%/year], respectively). These CMV effects were additive with those of cigarette smoking. No associations were found between CMV serology and FVC, indicating specific effects of CMV seropositivity on airflow limitation. Conclusion: High CMV serology in young to mid‐adult life may be linked to increased COPD risk through an accelerated decline of lung function. [ABSTRACT FROM AUTHOR]

The physiological importance of mucus plugs in computed tomography (CT) imaging is being increasingly recognized. However, whether airway inflammation and smoking affect the association between mucus plugs and clinical–physiological outcomes in asthma remains to be elucidated. The objective of this study is to examine how airway inflammation and/or smoking affect the correlation of CT-based mucus plug scores with exacerbation frequency and airflow limitation indices in asthma. A total of 168 patients with asthma who underwent chest CT and sputum evaluation were enrolled and classified in eosinophilic asthma (EA; n = 103) and non-eosinophilic asthma (NEA; n = 65) groups based on sputum eosinophil percentage (cut-off: 3%). The mucus plug score was defined as the number of lung segments with mucus plugs seen on CT. More mucus plugs were detected on CT scans in the EA group than in the NEA group, regardless of smoking status. Mucus plug score and exacerbation frequency during one year after enrollment were significantly associated in the EA group but not in the NEA group after adjusting for demographics, blood eosinophil count, and fractional exhaled nitric oxide. Mucus plug score was associated with percentage of predicted forced expiratory volume in 1 s in non-smoking individuals in the EA and NEA group and in smoking individuals in the EA group but not in the NEA group after adjusting for demographics. The association of mucus plug score with exacerbation frequency and reduced lung function may vary due to airway inflammatory profile and smoking status in asthma. [ABSTRACT FROM AUTHOR]

Background: Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations. Methods: In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed. Results: COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p < 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV1, FEV1/FVC, VC, and IC (all p < 0.05). For MMP-9, a positive correlation was found with RV/TLC% (p = 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (p = 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (p ≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found. Conclusions: COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity. [ABSTRACT FROM AUTHOR]

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

Background: We previously reported an association of high fat mass levels from age 9 to 15 years with lower forced expiratory flow in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years. Here, we aimed to assess whether insulin resistance and C‐reactive protein (CRP) at 15 years partially mediate this association. Methods: We included 2263 children from the UK Avon Longitudinal Study of Parents and Children population‐based cohort (ALSPAC). Four fat mass index (FMI) trajectories ("low," "medium‐low," "medium‐high," "high") from 9 to 15 years were previously identified using Group‐Based Trajectory Modeling. Data on CRP, glucose, insulin, and post‐bronchodilator FEV1/FVC were available at 15 years. We defined insulin resistance by the homeostasis model assessment‐estimated insulin resistance index (HOMA‐IR). We used adjusted linear regression models and a causal mediation analysis to assess the mediating role of HOMA‐IR and CRP. Results: Compared to children in the "low" FMI trajectory, children in the "medium‐high" and "high" FMI trajectories had lower FEV1/FVC at 15 years. The percentage of the total effect explained by HOMA‐IR was 19.8% [−114.1 to 170.0] and 20.4% [1.6 to 69.0] for the "medium‐high" and "high" trajectories, respectively. In contrast, there was little evidence for a mediating role of CRP. Conclusion: The association between mid‐childhood fat mass and FEV1/FVC ratio at 15 years may be partially mediated by insulin resistance. [ABSTRACT FROM AUTHOR]

Yanyan Xu,1 Tian Liang,2 Yanhui Ma,2 Sheng Xie,1 Hongliang Sun,2 Lei Wang,3 Yinghao Xu4 1Department of Radiology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Department of Radiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Beijing MicroVec. Inc., Beijing, People’s Republic of China; 4Canon Medical Systems, Beijing, People’s Republic of ChinaCorrespondence: Sheng Xie, Department of Radiology, Peking University China-Japan Friendship School of Clinical Medicine, Yinghua Street 2#, Chaoyang District, Beijing, People’s Republic of China, Tel +86 108-420-5855, Fax +86 1064222963, Email xs_mri@126.comPurpose: To quantitatively identify abnormal lung motion in chronic obstructive pulmonary disease (COPD) using strain analysis, and further clarify the potential differences of deformation in COPD with different severity of airflow limitation.Materials and Methods: Totally, 53 patients at high-risk for COPD were enrolled in this study. All CT examinations were performed on a 320-row MDCT scanner, and strain measurement based on dynamic-ventilation CT data was performed with a computational fluid dynamics analysis software (Micro Vec V3.6.2). The strain-related parameters derived from the whole expiration phase (PSmax-all, PSmean-all, Speedmax-all), the first 2s of expiration phase (PSmax2s, PSmean2s, Speedmax2s) were divided respectively by the changes in lung volume to adjust for the degree of expiration. Spearman rank correlation analysis was used to evaluate associations between the strain-related parameters and various spirometric parameters. Comparisons of the strain-related parameters between COPD and non-COPD patients, between GOLD I (mild airflow restriction) and GOLD II–IV (moderate to severe airflow restriction) were made using the Mann–Whitney U-test. Receiver-operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of the strain-related parameters for COPD. P < 0.05 was considered statistically significant.Results: Strain-related parameters demonstrated positive correlations with spirometric parameters (ρ=0.275∼ 0.687, P< 0.05), suggesting that heterogeneity in lung motion was related to abnormal spirometric results. Strain-related parameters can quantitatively distinguish COPD from non-COPD patients with moderate diagnostic significance with the AUC values ranged from 0.821 to 0.894. Furthermore, parameters of the whole expiration phase (PSmax-all, Speedmax-all) demonstrated significant differences (P=0.005; P=0.04) between COPD patients with mild and moderate to severe airflow limitation.Conclusion: Strain-related parameters derived from dynamic-ventilation CT data covering the whole lung associated with lung function changes in COPD, reflecting the severity of airflow limitation in some degree, even though its utility in severe COPD patients remains to be investigated.Keywords: strain analysis, dynamic-ventilation CT, chronic obstructive pulmonary disease, computed tomography, CT, airflow limitation

Sunyoung Kim,1 Hyoung Kyu Yoon,2 Chin Kook Rhee,3 Hee-Won Jung,4 Hyun Lee,5 Yong Suk Jo3 1Department of Family Medicine, College of Medicine, Kyung Hee University, Seoul, Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 4Division of Geriatrics, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 5Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, KoreaCorrespondence: Yong Suk Jo, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Tel +82-2-2258-6067, Fax +82-2-599-3589, Email lucidyonge@gmail.comBackground and Objective: Sarcopenia is mainly results from aging; however, it is more prevalent in chronic airway disease such as obstructive pulmonary disease (COPD). Hand grip strength (HGS) can be used as an indicator to evaluate sarcopenia. We aimed to assess the association between HGS and severity of airflow limitation (AFL) in the general population.Methods: We conducted a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2018. Subjects aged ≥ 40 years who underwent both spirometry and HGS tests were included. AFL was defined by spirometry revealed forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.70). A propensity score-matched comparison was performed, and the risk for moderate-to-very severe AFL was analyzed using logistic regression analysis.Results: Among 15,950 subjects, 2277 (14.3%) had AFL with mean FEV1 was 77.1% of the predicted value. Male was predominant in both individuals without AFL and with AFL (74.2% vs 73.5%, p = 0.613). The HGS was 32.9 ± 9.5 kg and 33.3 ± 9.5 kg in participants without AFL and with AFL (p = 0.109). However, HGS was significantly decreased as AFL getting more severe: 34.0 ± 9.6 kg in mild, 33.0 ± 9.5 kg in moderate, and 30.8 ± 8.5 kg in severe to very severe AFL group (p< 0.001). As HGS decreased, adjusted odds for moderate-to-very severe AFL increased compared to those with mild AFL (adjusted odds ratio [aOR], 0.97; 95% confidence interval [CI], 0.951– 0.987) and both without AFL and mild AFL group (aOR, 0.98; 95% CI, 0.967– 0.995) in age-, sex-, and body mass index (BMI)-matched comparisons.Conclusion: Lower HGS is significantly associated with moderate-to-very severe AFL in age-, sex-, and BMI-matched comparisons.Keywords: hand grip strength, airflow limitation, severity

Cuiqiong Dai,1,&ast; Zihui Wang,1,&ast; Huajing Yang,1,&ast; Shan Xiao,1 Jianwu Xu,1 Zhishan Deng,1 Fan Wu,1,2 Xiang Wen,1 Youlan Zheng,1 Lifei Lu,1 Ningning Zhao,1 Peiyu Huang,1 Yumin Zhou,1,2 Pixin Ran1,2 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Laboratory, Bio-Island, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin Ran; Yumin Zhou, Tel +86-20 3710 3616, Fax +86-20 81340482, Email pxran@gzhmu.edu.cn; zhouyumin410@126.comBackground: The potential protective role of serum total bilirubin (TB) for chronic obstructive pulmonary disease (COPD) is controversial. We aimed to investigate whether serum TB could prevent airflow limitation (reduce the risk of COPD) and whether these associations were causal or reversely causal.Methods: We conducted a multi-center and cross-sectional study including 3069 participants. Logistic regression model (LRM) with restricted cubic spline (RCS) and priori defined quintile categories were used to assess the associations of TB with COPD. Besides, ordinary least squares (OLS) regression model with RCS curves were applied to assess the dose-response relationship between serum TB and airflow limitation (FEV1/FVC). To verify the causal direction between TB and COPD, a bidirectional Mendelian randomization analysis was carried out with GWAS data from European ancestry.Results: In the cross-sectional study, the relationship between levels of TB and COPD risk was U shaped (P=0.001), and the low and high concentrations of TB apparently increasing the risk of COPD (OR 1.40, 95% CI 1.07 to 1.82 for less than 9 μmol/L; OR 1.36, 95% CI 1.06 to 1.76 for 9.01– 1 0.88 μmol/L; OR 1.50, 95% CI 1.16 to 1.95 for more than 13 μmol/L). There was a significant non-linear relationship between TB and FEV1/FVC (non-linear p=0.004). Furthermore, results of bidirectional Mendelian randomization analysis (OR 1.000; 95% CI 0.983 to 1.017 for MR and OR 0.998; 95% CI 0.976 to 1.020 for reversal MR) did not support the causal effects between serum TB and FEV1/FVC after controlling the effect of potential confounders and revised causality.Conclusion: Our study reveals that there was non-linear does-response pattern between serum TB and COPD. However, there was little evidence for the linear causal associations of serum TB with airflow limitation. The relationship of TB with COPD needs further study and careful interpretation.Keywords: total bilirubin, COPD, airflow limitation, Mendelian randomization analysis

Ruolin Mao,1,&ast; Zilong Liu,1,&ast; Yunfeng Zhao,2,&ast; Chunlin Du,3,&ast; Jintao Zhou,4,&ast; Qian Wang,5,&ast; Jinchang Lu,3 Lei Gao,1 Bo Cui,1 Yuan Ma,1 Tieying Sun,6 Lei Zhu,1,7 Zhihong Chen1 1Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University. Shanghai Institute of Respiratory Disease, Shanghai, People’s Republic of China; 2Department of Respiratory Disease, Punan Hospital, Pudong New Area, Shanghai, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Taicang Hospital Affiliated with Soochow University, Taicang, Jiangsu, People’s Republic of China; 5Department of Respiratory Medicine, Jing’an District Zhabei Central Hospital, Shanghai, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Chen;Tieying Sun Tel +86-21-64041990-2445; +86-10-85132266Fax +86-21-64187165; +86-10-65132969Email chen.zhihong@zs-hospital.sh.cn; suntieying@126.comBackground: Early diagnosis and proper management of a large number of chronic obstructive pulmonary disease (COPD) patients are great challenges for the Chinese health care system. Although tiered medical services have been promoted by the Chinese government since 2015, they have not been ideally implemented for COPD diagnosis and management.Patients and Methods: We designed a cross-sectional study. Eligible COPD patients (n = 648) and physicians (n = 161) were consecutively recruited from 8 hospitals in different tiers in China. COPD characteristics and treatments were compared among hospitals in different tiers. Multivariate logistic regression was performed to identify risk factors associated with airflow limitation, symptoms and acute exacerbation.Results: The PFT rate at first diagnosis was 99%, 69.4% and 29.9% in teaching, second-tier and community hospitals (P < 0.001). Only approximately 10.9%, 1.7% and 9.6% and 21.8%, 6.9% and 32% of COPD patients received influenza or pneumococcal vaccines (P < 0.001). The proportion of patients who did not use inhaled drugs or had irregular inhalation was 2%, 24.6% and 78.8% (P < 0.001). Education level (RR-1 = − 41.26%, P = 0.007), FEV1%pred (RR-1 = − 2.76%, P < 0.001), and influenza vaccination in the last year (RR-1 = − 64.53%, P = 0.006) were all negatively correlated with COPD acute exacerbation (AE). COPD duration (RR-1 = 131.73%, P = 0.009), AE (RR-1 = 151.39%, P < 0.001), and COPD Assessment Test (CAT) scores (RR-1 = 3.82%, P = 0.019) were all positively correlated with COPD airflow limitation severity.Conclusion: Differences exist in the diagnosis, treatment and management of COPD among different tiers of hospitals in China. Teaching hospitals can manage COPD patients relatively well. There are still some gaps compared with developed countries.Keywords: stable chronic obstructive pulmonary disease, tiered medical system, airflow limitation, symptoms, acute exacerbation

Toshihiko Kaise,1 Eishin Sakihara,2 Kentaro Tamaki,3 Hiroaki Miyata,4 Norimichi Hirahara,4 Oksana Kirichek,5 Ryosuke Tawara,1 Shoko Akiyama,1 Masayuki Katsumata,1 Mei Haruya,6 Takeo Ishii,7 Edgar P Simard,8 Bruce E Miller,8 Ruth Tal-Singer8 1Japan Development, GSK, Tokyo, Japan; 2Lifestyle Related Disease Medical Center, Naha Medical Association, Okinawa, Japan; 3Department of Breast Surgery, Nahanishi Clinic, Okinawa, Japan; 4Health Policy and Management, School of Medicine, Keio University, Tokyo, Japan; 5Value Evidence and Outcomes, GSK, Stockley Park, UK; 6Government Affairs and Market Access, GSK, Tokyo, Japan; 7Medical Japan, GSK, Tokyo, Japan; 8Value Evidence and Outcomes, GSK, Collegeville, PA, USACorrespondence: Toshihiko KaiseJapan Development, GSK, Tokyo, JapanTel +81 80 5927 9500Fax +81 3 4231 5993Email toshihiko.kaise@gsk.comPurpose: Many individuals with obstructive airway disease (OAD), including chronic obstructive pulmonary disease (COPD) and asthma, remain undiagnosed, despite the potential for reducing disease burden through early detection and treatment. OCEAN aimed to determine the prevalence of, and characteristics associated with, impaired lung function in a Japanese population, with the goal of improving strategies for early OAD detection.Methods: OCEAN was an observational, cross-sectional study in sequentially recruited Japanese individuals ≥ 40 years of age undergoing routine health examinations. Participants completed screening questionnaires and spirometry testing. Airflow limitation was defined as forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.7 by pre-bronchodilator spirometry. Preserved ratio impaired spirometry (PRISm) was defined as FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted. The primary endpoint was prevalence of spirometry-based airflow limitation and PRISm. The characteristics of study participants were reported as secondary endpoints.Results: Overall, 2518 individuals were included; 79% were < 60 years of age (mean 52.0 years). Airflow limitation and PRISm were observed in 52 (2.1%) and 420 (16.7%) participants, respectively. FEV1 in the PRISm group was between that in the no airflow limitation/PRISm and airflow limitation groups, FVC was similar in the PRISm and airflow limitation groups. The PRISm group had higher mean body mass index and a higher proportion of comorbid metabolic disease compared with the airflow limitation group. The prevalence of airflow limitation and PRISm was highest among current smokers (3.9% and 21.3%, respectively) versus former or never smokers.Conclusion: A significant proportion of Japanese individuals < 60 years of age attending their annual health examination had impaired lung function (airflow limitation and PRISm); prevalence was highest among current smokers. These findings support screening of current or former smokers ≥ 40 years of age using patient-reported questionnaires to inform the need for spirometry to confirm an OAD diagnosis.Keywords: CAPTURE, CAAT, PRISm, COPD-Q, Japan, airflow limitation

Shuyun Chen,1,2,&ast; Xiaochen Li,1,3,&ast; Zihui Wang,1,&ast; Yumin Zhou,1 Dongxing Zhao,1 Zhuxiang Zhao,1,4 Sha Liu,1 Pixin Ran1 1State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, National Clinical Research Center for Respiratory Disease Guangzhou, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 3The People’s Hospital of Hubei Province, Wuhan, Hubei Province, People’s Republic of China; 4The First People’s Hospital of Guangzhou City, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin RanState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, National Clinical Research Center for Respiratory Disease Guangzhou, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No. 195 Dongfeng Xi Road, Guangzhou, 510000, Guangdong Province, People’s Republic of ChinaTel +86 2083205187Email pxran@gzhmu.edu.cnPurpose: The use of simple and affordable screening tools for chronic obstructive pulmonary disease (COPD) is limited. We aimed to assess the validity of a handheld expiratory flowmeter (Vitalograph Ltd., COPD-6®, Ireland) for COPD screening in Chinese primary care settings.Methods: In our cross-sectional study, subjects were randomly selected in eight primary care settings. Tests with the handheld expiratory flowmeter and the conventional spirometry were sequentially performed on all participants. The correlation between the handheld expiratory flowmeter and the conventional spirometry was determined. Validity was determined by the area under the receiver operator characteristic curve (AUC) of the forced expiratory volume in one second (FEV1)/forced expiratory volume in six seconds (FEV6) that used to detect airway obstruction. The sensitivity, specificity, predictive values, and likelihood ratio were calculated according to different FEV1/FEV6 cut-off points.Results: A total of 229 subjects (15.4%) were diagnosed with airflow limitation by conventional spirometry. FEV1, FEV6, and FEV1/FEV6 measured by the handheld expiratory flowmeter were correlated with FEV1, FVC, and FEV1/FVC measured by the conventional spirometry (r=0.889, 0.835 and 0.647, p< 0.001), respectively. AUC of the FEV1/FEV6 to determine airflow obstruction was 0.857 (95% CI: 0.826 to 0.888). No significant difference of AUC was observed between the symptomatic group and the asymptomatic group (AUC=0.869 vs 0.843, P=0.425). A similar phenomenon was found in the AUC of smokers and never-smokers (AUC=0.862 vs 0.840; P=0.515). The cut-off point for FEV1/FEV6 was 0.77 and the corresponding sensitivity and specificity were 71.2% and 89.8%, respectively.Conclusion: The handheld expiratory flowmeter might be used as a screening device for COPD in Chinese primary care settings.Keywords: COPD screening, airflow limitation, FEV1, FEV6, lung function

Maéva Zysman,1 Gaëtan Deslee,2 Thierry Perez,3 Pierre-Régis Burgel,4 Olivier Le Rouzic,3 Graziella Brinchault-Rabin,5 Pascale Nesme-Meyer,6 Isabelle Court-Fortune,7 Gilles Jebrak,8 Pascal Chanez,9 Denis Caillaud,10 Jean-Louis Paillasseur,11 Nicolas Roche4 1Pulmonary Department, Pôle Cardio-thoracique, CHU Haut-Lévèque, INSERM U1045, Bordeaux, France; 2Pulmonary Department, Maison Blanche University Hospital, INSERM U01250, Reims, France; 3University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL - Center for Infection and Immunity of Lille, Lille, France; 4Respiratory Medicine, Cochin Hospital, AP-HP and Université de Paris, Institut Cochin, INSERM U1016, Paris, France; 5Service de Pneumologie, Hôpital Pontchaillou, Rennes, France; 6Service de Pneumologie, Hôpital de la Croix-Rousse, Lyon, France; 7Service de Pneumologie, CHU Saint Etienne, Saint Etienne, France; 8Service de Pneumologie, Hôpital Bichat, AP-HP, Paris, France; 9Département des Maladies Respiratoires, AP-HM, Université de la Méditerranée, Marseille, France; 10Service de Pneumologie, Hôpital Gabriel Montpied, CHU, Clermont-Ferrand, France; 11EFFI-STAT, Paris, FranceCorrespondence: Maéva ZysmanAvenue de Magellan, Service des Maladies Respiratoires, CHU Haut Lévèque, Pessac, 33600, FranceTel +33 5 56 79 56 79Email maeva.zysman@chu-bordeaux.frBackground: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1< 50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood.Methods: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02< 60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes).Results: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥ 60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02< 60 mmHg and FEV1< 50% (n=115, 13%), those with severe hypoxemia but FEV1≥ 50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification.Conclusion: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes.Trial Registration: 04– 479.Keywords: chronic obstructive pulmonary disease, severe hypoxemia, airflow limitation

Kazuhiko Watanabe,1 Ayumi Onoue,2 Hisamitsu Omori,2 Kenichi Kubota,3 Minoru Yoshida,3 Takahiko Katoh1 1Department of Public Health, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 3Japanese Red Cross Kumamoto Health Care Center, Kumamoto, JapanCorrespondence: Hisamitsu OmoriDepartment of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, 4-24-1 Kuhonji, Chuo-ku Kumamoto, 862-0976, JapanTel/Fax +81-96-373-5462Email omorih@gpo.kumamoto-u.ac.jpPurpose: This study aimed to reveal the association between airflow limitation (AL) and carotid intima-media thickness (IMT) according to smoking status in Japan.Subjects and Methods: This cross-sectional study was performed in 2809 subjects, who underwent a comprehensive health examination with pulmonary function tests and carotid ultrasonographic measurement. AL was defined as forced expiratory volume in 1 s/forced vital capacity of < 0.7. The subjects were divided into the following four groups: never smokers without AL, never smokers with AL, former/current smokers without AL, and former/current smokers with AL. Mean IMT, the maximum measurable IMT value in the left and right common carotid arteries (IMT-C max), and mean IMT-C max were measured by carotid ultrasonography. The carotid wall thickness as defined as follows: IMT ≥ 1.1 mm (IMT1.1), IMT-C max ≥ 1.2 mm (IMTc1.2), and IMT-C max > 1.5 mm (IMTc1.5), based on each measured region. The association between AL and the carotid wall thickness according to smoking status was assessed by logistic regression analysis.Results: The mean carotid IMT and mean IMT-C max were significantly higher in never smokers with AL and former/current smokers with or without AL than in never smokers without AL. In logistic regression models adjusted for sex, age, body mass index, hypertension, dyslipidemia, hyperglycemia, physical activity, and alcohol consumption, the risk of carotid wall thickness (IMT1.1 [odds ratio {OR}: 1.55; 95% confidence interval {CI}: 1.07– 2.24]; IMTc1.2 [OR: 1.52; 95% CI: 1.03– 2.24]; IMTc1.5 [OR: 1.99; 95% CI: 1.15– 3.46]) were significantly higher in former/current smokers with AL than in never smokers without AL.Conclusion: The present results suggest that greater IMT and risk of carotid wall thickness were associated with AL and smoking experience.Keywords: chronic obstructive pulmonary disease, cardiovascular disease, comorbidity, atherosclerosis, airflow limitation, carotid intima-media thickness

Objective: To establish the prevalence of upper airway resistance syndrome (UARS) according to different diagnostic criteria and evaluate its epidemiological characteristics in a representative sample of a large urban center.Methods: This was a single-center evaluation involving volunteers from EPISONO, an epidemiological study focused on sleep disturbances and related factors in adults from São Paulo, Brazil in 2007.Results: Considering the diagnostic criteria for UARS to be an apnea-hypopnea index of <5 events/h, minimum SpO2 ≥ 92%, the presence of airflow limitation during sleep for ≥5% of total sleep time, and daytime symptoms (sleepiness and/or fatigue), we observed a prevalence of the condition of 3.1% (4.4% in women and 1.5% in men).Conclusions: Although the diagnostic criteria for UARS, or even its existence as a syndrome, are still a subject of debate in the literature, the findings from this epidemiological study highlights UARS as a non-hypoxic sleep-disordered breathing condition with a significant prevalence in the general population, being more frequent among female young adults. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the changes of body surface temperature of stable chronic obstructive pulmonary disease (COPD) patients and explore its clinical significance for the progression of COPD. The aim of this study was to explore the correlation between body surface temperature and disease severity in COPD patients. From May 2015 to May 2016, the patients who were diagnosed as COPD at stable phase (n = 148) were enrolled in this study. The subjects in control group (n = 49) were healthy people. The patients' general condition modified Medical Research Council (mMRC) dyspnea scale and the COPD assessment test (CAT) score were recorded, and pulmonary function of patients was determined. Back average temperature measurement was made using a thermal infrared imager (DT-9875, CEM, China). Patients in the COPD group had significantly lower mean temperatures of the back than those in the control group. The mean temperature of the back presented a decreased tendency with the aggravation of airflow limitation. Correlation analysis revealed that in the COPD group, the back temperature was negatively correlated with smoking index and mMRC score. FEV1%, FVC% and FEV1/FVC were positively correlated with pulmonary function. Smoking showed a tendency to lower the back temperature of COPD patients. This study preliminarily suggested that the body surface temperature of COPD patients decreased compared with that of healthy people, which may be associated with the dysfunction of autonomic nerve, increased basal metabolic rate, metabolic syndrome and peripheral nerve injury in COPD patients. • Body surface temperature of COPD patients decreased compared with that of healthy people. • Body surface temperature of COPD patients may be associated with dysfunction of autonomic nerve. • Body surface temperature of COPD patients may be associated with increased basal metabolic rate. • Body surface temperature of COPD patients may be associated with metabolic syndrome. • Body surface temperature of COPD patients may be associated with peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Martina Sundqvist,1,* Kristina Andelid,2,* Ann Ekberg-Jansson,3 Johan Bylund,4 Anna Karlsson-Bengtsson,1,5 Anders Lindén6,7 1Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2COPD Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 5Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; 6Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 7Karolinska Severe COPD Center, Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden*These authors contributed equally to this workCorrespondence: Martina SundqvistDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, Gothenburg, S-413 46, SwedenEmail martina.sundqvist@rheuma.gu.sePurpose: The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations.Patients and Methods: The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth.Results: When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with HNS or LTS. Nor did this level of Galectin-3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations.Conclusion: Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting.Keywords: COPD, CRP, airflow limitation, exacerbation

BackgroundInfluenza vaccination is strongly recommended for people with chronic lung diseases, including chronic obstructive pulmonary disease, to reduce risk of exacerbation. We assess the influenza vaccination rate and its related factors in participants with airflow limitation (AFL) using nationally representative data in Korea.MethodsWe conducted a cross-sectional study from the Korea National Health and Nutrition Examination Survey from 2007 to 2018. Individuals ≥ 40 years who underwent spirometry and had identifiable information on influenza vaccination status were included.ResultsOverall influenza vaccination coverage was 61.2% in participants with AFL and 41.8% in participants without AFL. Age had a significant impact on the yearly vaccination rate in participants with AFL. Over the 10 years of study period, while the yearly vaccination rate steadily increased from 58.3 to 61.9% in elderly participants (≥65 years) with AFL (p for trend = 0.117), the yearly vaccination rate decreased from 41.5% to 30.8% in younger participants (

Background The Associations between vascular disease and ABO blood groups have a long history, but no consensus exists regarding its magnitude and significance, or whether it relates to all disorders equally. This study was conducted to establish a relation between risk for central retinal vein occlusion and ABO blood groups. Materials and Methods This study was a hospital based comparative, observational study conducted in the Department of Ophthalmology, SKIMS Medical College Hospital, Srinagar from 2020 to 2022. 58 patients above the age of 18 years were included in the study, 28 patients with established CRVO who attended the ophthalmology opd were included in the case group and 30 age and sex matched patients without any retinal disease were included in the control group. All the patients underwent a detailed ophthalmological examination, systemic diseases and demographic characteristics were recorded. In all these patients ABO blood grouping was done. The blood groups of the patients were divided into 2 groups as O and non-O. A, B and AB blood groups were defined as non-O. Results out of a total of 58 patients 28 were included in the case group with CRVO and 30 were in the control group. In the case (CRVO) group, non-O blood type was found in 23(82.14%) patients and the O blood type was found in 5(17.85%) patients. In the control group non-O blood type was seen in 15(50%) of the patients and O blood type was seen in 15(50%) patients. Non-O type blood group was significantly higher in the group with CRVO (p < 0.05), which is statistically significant. Conclusion Our study revealed that the frequency of non-O blood groups was significantly higher in patients with CRVO as compared to the control patients. Thus showing that non-O blood groups are at an increasing risk of developing retinal vascular occlusion. [ABSTRACT FROM AUTHOR]

Rationale: Determining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment. Objectives: Here we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies. Methods: From five nocturnal polysomnography signals (airflow, thoracic and abdominal effort, oxygen saturation, and snore), nine features were extracted and weighted to derive the breath-by-breath probability of obstruction (Pobs). A development and initial test set of 29 subjects (development = 6, test = 23) (New York, NY) and a second test set of 39 subjects (Solingen, Germany), both with esophageal manometry, were used to develop Pobs and validate it against gold-standard upper airway resistance. A separate dataset of 114 subjects with 2 consecutive nocturnal polysomnographies (New York, NY) without esophageal manometry was used to assess the night-to-night variability of Pobs. Measurements and Main Results: A total of 1,962,229 breaths were analyzed. On a breath-by-breath level, Pobs was strongly correlated with normalized upper airway resistance in both test sets (set 1: cubic adjusted [adj.] R2 = 0.87, P < 0.001, area under the receiver operating characteristic curve = 0.74; set 2: cubic adj. R2 = 0.83, P < 0.001, area under the receiver operating characteristic curve = 0.7). On a subject level, median Pobs was associated with the median normalized upper airway resistance (set 1: linear adj. R2 = 0.59, P < 0.001; set 2: linear adj. R2 = 0.45, P < 0.001). Median Pobs exhibited low night-to-night variability [intraclass correlation(2, 1) = 0.93]. Conclusions: Using nearly 2 million breaths from 182 subjects, we show that breath-by-breath probability of obstruction can reliably predict the overall burden of obstructed breaths in individual subjects and can aid in determining the type of sleep apnea. [ABSTRACT FROM AUTHOR]

Andras Bikov,1,2 Peter Lange,3,4 Julie A Anderson,5 Robert D Brook,6 Peter MA Calverley,7 Bartolome R Celli,8 Nicholas J Cowans,9 Courtney Crim,10 Ian J Dixon,9 Fernando J Martinez,11 David E Newby,12 Julie C Yates,10 Jørgen Vestbo1,2 1Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 2Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 3Medical Department, Herlev and Gentofte Hospital, Herlev, Denmark; 4Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 5Research & Development, GlaxoSmithKline, Middlesex, UK; 6University of Michigan Health System, Ann Arbor, MI, USA; 7University of Liverpool, Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK; 8Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 9Statistics & Programming, Veramed Ltd., Twickenham, UK; 10Research & Development, GlaxoSmithKline, Research Triangle Park, NC, USA; 11Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, USA; 12British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UKCorrespondence: Andras Bikov 2nd Floor ERC Building, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UKTel +36203141599Fax +441612915730Email andras.bikov@gmail.comPurpose: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations. However, it is unclear if forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differ in predictive value.Patients and Methods: Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed. Patients were grouped into quintiles for each lung function parameter (FEV1 %predicted, FVC %predicted, FEV1/FVC). The four highest quintiles (Q2–Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations. Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.Results: Compared to Q1 (< 53.5% FEV1 predicted), increasing FEV1 quintiles (Q2 53.5– 457.5% predicted, Q3 57.5– 461.6% predicted, Q4 61.6– 465.8% predicted, and Q5 ≥ 65.8%) were all associated with significantly decreased all-cause mortality (20% (4– 34%), 28% (13– 40%), 23% (7– 36%), and 30% (15– 42%) risk reduction, respectively). In contrast, a significant risk reduction (21% (4– 35%)) was seen only between Q1 and Q5 quintiles of FVC. Neither FEV1 nor FVC was associated with cardiovascular risk. Increased FEV1 and FEV1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8– 52%) risk increase).Conclusion: Our results suggest that FEV1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks.Keywords: airflow limitation, cardiovascular risk, exacerbation, lung function, lung volumes, death rate

Mutsuo Yamaya,1 Osamu Usami,2 Shoichi Nakayama,3 Naoki Tode,4 Aya Yamada,5 Shunsuke Ito,2 Fumiya Omata,2 Haruki Momma,5 Masakatsu Funakubo,6 Masakazu Ichinose4 1Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; 2Department of Respiratory Medicine, Kurihara Central Hospital, Kurihara 987-2205, Japan; 3Department of Medicine, Kurihara Central Hospital, Kurihara 987-2205, Japan; 4Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; 5Department of Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; 6Department of Radiology, Kurihara Central Hospital, Kurihara 987-2205, JapanCorrespondence: Mutsuo YamayaDepartment of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanTel +81-22-717-7184Fax +81-22-717-7576Email myamaya@med.tohoku.ac.jpBackground: 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 (FEV1), the FEV1/FVC ratio (FEV1/FVC), the percent predicted values of FEV1 (%FEV1), 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, FEV1, FEV1/FVC and %FEV1; 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 FEV1. 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, FEV1, 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.Keywords: malnutrition, chronic obstructive pulmonary disease, exacerbation, severe emphysema, airflow limitation